BASE-MODIFIED RIBONUCLEOSIDES AS PRODRUGS AGAINST VIRAL AND BACTERIAL INFECTIONS STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT [0001] This invention was made with Government support of the project “Setting a New Standard for VEEV mAb Therapeutics” (NB-33690) awarded by the DTRA funding. The Government has certain rights in this invention. BACKGROUND [0002] Chemotherapy remains a major component of treatment of cancer and infectious diseases. In the past 60 years, nucleoside analogs, also called antimetabolites, have had a substantial positive impact on the treatment of human neoplastic formations, particularly hematological, but also including lung, breast, and prostate cancer, which remain the top three deadliest malignancies. Structural similarity of the antimetabolites to physiological nucleosides allows their passage into cells by nucleoside transporters, where they are metabolized into 5'-phosphates, the active species which interfere with a large variety of intracellular targets or viruses infiltrating the cells. In particular, they inhibit enzymes involved in the synthesis of nucleic acids and nucleotides, signal for DNA damage upon incorporation, obstruct DNA repair and phosphorylation of proteins responsible for signaling for cellular proliferation, and trigger apoptosis by directly affecting mitochondria. Not surprisingly, the most active clinically approved antimetabolite anticancer drugs, such as gemcitabine or 5-fluorouracil, can exhibit fatal side effects, as they also affect rapidly proliferating normal human cells, lymphocytes, and sometimes even non-dividing cells, such as neurons, which substantially lowers their safety index. Combined administration of the best known antimetabolites with antibodies, marine-derived lipids, inhibitors of tyrosine kinases or nucleoside transporters has so far resulted in a moderate treatment improvement at best, but has sometimes proven to be counter-productive. Likewise, limiting the side effects of antiviral drugs, including potential agents against SARS-CoV-2 and COVID- 19, remains a challenge For instance favipiravir an agent having a therapeutic effect on SARS-CoV-2, is suspected of causing cholestatic liver injury. Dolutegravir, an integrase strand transfer inhibitor that is widely used to treat HIV, is implicated in neuropsychiatric side effects, while tenofovir disoproxil fumarate (TDF), an agent for treatment of chronic hepatitis B, appears to adversely affect renal function. The design of efficient nanocarriers purposed to reduce the off-target effects of antiviral agents still remains in the early stages of development. [0003] Nucleoside and nucleobase analogs capable of interfering with nucleic acid synthesis have played essential roles in the fight against cancer and infectious diseases for more than six decades. However, many of these agents are associated with significant and potentially lethal off-target intracellular effects that limit their use. In this regard, N4-hydroxycytidine (NHC), having Structure I, exhibits promising activity against the New World alphaviruses, e.g, Venezuelan, Eastern, and Western equine encephalitis viruses (VEEV, EEEV and WEEV, respectively), Ebola, Marburg, norovirus, as well as respiratory infections, most notably, SARS-CoV-2 and COVID-19. However, mutagenic properties of NHC substantially limit its potential to become a drug. Structure I [0004] Based on the ability of certain base-modified single nucleotide probes to terminate DNA synthesis, it was later discovered that certain nucleoside analogs of those nucleotides can serve as pro-drugs that are active against several cancer cell lines, while showing lower toxicity toward normal cells compared to current antimetabolite chemotherapeutics. An example is Cidofovir, having Structure II.

Structure II [0005] Similarly, a hit compound, having Structure III, inhibiting replication of human papilloma virus (HPV) was revealed whose efficiency was higher and cytotoxicity was lower than that of cidofovir, a known antiviral drug. Structure III [0006] Since the mutagenic properties of NHC substantially limit its potential to become a drug a need exists for new molecular structure that would result in the development of a novel anti-RNA viral lead nucleosides with an improved therapeutic potential compared to that of NHC. [0007] The discussion of shortcomings and needs existing in the field prior to the present invention is in no way an admission that such shortcomings and needs were recognized by those skilled in the art prior to the present disclosure. BRIEF DESCRIPTION OF THE FIGURES [0008] Many aspects of this disclosure can be better understood with reference to the following figures. [0009] Figure 1 is an example according to various embodiments, illustrating the bioactivity of a compound having Structure IV (RIID1271) and control (NHC) compounds. [0010] Figure 2 is an example according to various embodiments, illustrating the cytotoxicity a compound having Structure IV (RIID1271) and control (NHC) compounds. [0011] It should be understood that the various embodiments are not limited to the examples illustrated in the figures. DETAILED DESCRIPTION Introduction and Definitions [0012] This disclosure is written to describe the invention to a person having ordinary skill in the art, who will understand that this disclosure is not limited to the specific examples or embodiments described. The examples and embodiments are single instances of the invention which will make a much larger scope apparent to the person having ordinary skill in the art. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by the person having ordinary skill in the art. It is also to be understood that the terminology used herein is for the purpose of describing examples and embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be limited only by the appended claims. [0013] All the features disclosed in this specification (including any accompanying claims, abstract, and drawings) may be replaced by alternative features serving the same, equivalent, or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features. The examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to the person having ordinary skill in the art and are to be included within the spirit and purview of this application. Many variations and modifications may be made to the embodiments of the disclosure without departing substantially from the spirit and principles of the disclosure. All such modifications and variations are intended to be included herein within the scope of this disclosure. For example, unless otherwise indicated, the present disclosure is not limited to particular materials, reagents, reaction materials, manufacturing processes, or the like, as such can vary. It is also to be understood that the terminology used herein is for purposes of describing particular embodiments only and is not intended to be limiting. It is also possible in the present disclosure that steps can be executed in different sequence where this is logically possible. [0014] All numeric values are herein assumed to be modified by the term “about,” whether or not explicitly indicated. The term “about” generally refers to a range of numbers that one of skill in the art would consider equivalent to the recited value (for example, having the same function or result). In many instances, the term “about” may include numbers that are rounded to the nearest significant figure. [0015] In everyday usage, indefinite articles (like “a” or “an”) precede countable nouns and noncountable nouns almost never take indefinite articles. It must be noted, therefore, that, as used in this specification and in the claims that follow, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a support” includes a plurality of supports. Particularly when a single countable noun is listed as an element in a claim, this specification will generally use a phrase such as “a single.” For example, “a single support.” [0016] In this specification and in the claims that follow, reference will be made to a number of terms that shall be defined to have the following meanings unless a contrary intention is apparent. [0017] As used herein, the term “standard temperature and pressure” generally refers to 25°C and 1 atmosphere. Standard temperature and pressure may also be referred to as “ambient conditions.” Unless indicated otherwise, parts are by weight, temperature is in °C, and pressure is at or near atmospheric. The terms “elevated temperatures” or “high-temperatures” generally refer to temperatures of at least 100°C. [0018] Unless otherwise specified, all percentages indicating the amount of a component in a composition represent a percent by weight of the component based on the total weight of the composition. The term “mol percent” or “mole percent” generally refers to the percentage that the moles of a particular component are of the total moles that are in a mixture. The sum of the mole fractions for each component in a solution is equal to 1. [0019] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit (unless the context clearly dictates otherwise), between the upper and lower limit of that range, and any other stated or intervening value in that stated range, is encompassed within the disclosure. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure. [0020] All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference and are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present disclosure is not entitled to antedate such publication by prior disclosure. Further, the dates of publication provided could be different from the actual publication dates that may need to be independently confirmed. [0021] For molecules having isomers or exhibiting one or more chiral centers only one of the possible variations may be shown for the sake of brevity. A person having ordinary skill in the art will appreciate that disclosure of all such variations is intended. When a specific variation is preferred, this disclosure will so state. [0022] Various embodiments are described by reference to chemical structures. In the chemical structures various chemical moieties are represented by R-groups. Some R-groups are described by reference to another chemical structure. A wavy bond line in a structure representing an R-group indicates the point at which the R-group is attached to or bonded to the main structure. In some chemical structures various cyclic moieties are represented by lettered rings. The lettered ring may represent a variety of cyclic structures. Some cyclic structures are described by reference to another chemical structure. A wavy bond line in a structure representing a cyclic structure indicates a bond that is shared with the main structure, or the point at which the cyclic structure is fused to the main structure to form a polycyclic structure. Various subscripts are also used. Each R-group has a numeric subscript which distinguishes it from other R-groups. R-groups and lettered rings may also include a lowercase alphabetical subscript, indicating that different embodiments, may have differing numbers of that moiety. If a lowercase alphabetical subscript may be 0, it means that, in some embodiments, the moiety may not be present. A dashed line in a cyclic structure indicates that in various embodiments one or more double-bounds may be present. When a compound may include more than one instance of a moiety, for example a moiety represented by an R-group, and that moiety is described as being “independently selected” from a list of options, each instance may be selected from the complete list without respect to any prior selections from the list; in other words, the instances may be the same or different and the same list item may be selected for multiple instances. Some R-group substitutions indicate a range, such as C1 – C6 alkyl. Such a range indicates that the R-group may be a C1 alkyl, a C2 alkyl, a C3 alkyl, a C4 alkyl, a C5 alkyl, or a C6 alkyl. In other words, all such ranges are intended to include an explicit reference to each member within the range. [0023] The term “co-administration” or “co-administering” as used herein refer to the administration of a substance before, concurrently, or after the administration of another substance such that the biological effects of either substance overlap. [0024] As used herein, the terms "reduce" and "inhibit" are used together because it is recognized that, in some cases, a decrease can be reduced below the level of detection of a particular assay. As such, it may not always be clear whether the expression level or activity is "reduced" below a level of detection of an assay, or is completely "inhibited." [0025] As used herein, "treatment" or "treating" means to administer a composition to a subject or a system with an undesired condition. The condition can include a disease (including infection) or disorder. "Prevention" or "preventing" means to administer a composition to a subject or a system at risk for the condition, and therefore includes preventing disease progression in symptomatic or asymptomatic subjects. The condition can include a predisposition to a disease or disorder. The effect of the administration of the composition to the subject (either treating and/or preventing) can be, but is not limited to, the cessation of one or more symptoms of the condition, a reduction or prevention of one or more symptoms of the condition, a reduction in the severity of the condition, the complete ablation of the condition, a stabilization or delay of the development or progression of a particular event or characteristic, or minimization of the chances that a particular event or characteristic will occur. [0026] As used herein in the context of viral infection, the term “therapeutically effective amount” refers to an amount of a composition of the disclosure that when administered to a human subject in need thereof, is sufficient to effect treatment or prophylaxis for virus infection. The amount that is therapeutically effective will depend upon the patient's size and gender, the stage and severity of the infection and the result sought. The full therapeutic effect does not necessarily occur by administration of one dose and may occur only after administration of a series of doses. Thus, a therapeutically effective amount may be administered in one or more administrations per day for successive days. For a given patient and condition, a therapeutically effective amount can be determined by methods known to those of skill in the art. For example, in reference to the treatment of a viral infection (e.g. alphavirus) infection using the compositions of the present disclosure, a therapeutically effective amount refers to that amount of the composition which has the effect of (1) reducing the shedding of the virus, (2) reducing the duration of the infection, (3) reducing infectivity and/or, (4) reducing the severity (or, preferably, eliminating) one or more other symptoms associated with the infection such as, for example, fever, headache, fatigue, dry cough, sore throat, respiratory distress, muscle aches, conjunctivitis, runny and/or stuffy nose. Such an effective dose will generally depend on the factors described above. A prophylactically effective dose is one that reduces the likelihood of contracting a virus infection. [0027] As used herein, the terms "subject" and "patient" are used interchangeably. As used herein, the term "subject" refers to an animal, preferably a mammal such as a non-primate (e.g., cows, pigs, horses, cats, dogs, rats etc.) and a primate (e.g., monkey and human), and most preferably a human. In some embodiments, the subject is a non-human animal such as a farm animal (e.g., a horse, pig, or cow) or a pet (e.g., a dog or cat). In a specific embodiment, the subject is an elderly human. In another embodiment, the subject is a human adult. In another embodiment, the subject is a human child. In yet another embodiment, the subject is a human infant. [0028] The terms “treat” “treating” or “treatment of” as used herein refers to providing any type of medical management to a subject. Treating includes, but is not limited to, administering a composition comprising one or more active agents to a subject using any known method. for purposes such as curing, reversing, alleviating, reducing the severity of, inhibiting the progression of, or reducing the likelihood of a disease, disorder, or condition or one or more symptoms or manifestations of a disease, disorder or condition. The administration of the drug can be oral, nasal, parental, topical, ophthalmic, or transdermal administration or delivery in the form of solid, semi-solid, lyophilized powder, or liquid dosage forms. The dosage forms include tablets, capsules, troches, powders, solutions, suspensions, suppositories, or the like, preferably in unit dosage forms suitable for simple administration of precise dosages. [0029] As used herein, the term “pharmaceutically acceptable salt” refers to those salts which retain the biological effectiveness and properties of the active ingredient of the biochemical composition, which are not otherwise undesirable. Pharmaceutically acceptable salts include, but are not limited to, salts formed after combination of the amine compound with inorganic acids like hydrochloric acid, or organic carboxylic acids such as oxalic acid or acetic acid to form oxalate or acetate salts, respectively. The pharmaceutically acceptable carrier may include pharmaceutically-acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting the compositions of the invention from one organ, or portion of the body, to another organ, or portion of the body without affecting its biological effect. Each carrier should be “acceptable” in the sense of being compatible with the other ingredients of the composition and not injurious to the subject. The novel bioactive nucleosides disclosed herein can be provided as a pharmaceutically acceptable salt. [0030] The term, “pharmaceutically acceptable carrier” as used herein means a pharmaceutically-acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting the compositions of the invention from one organ, or portion of the body, to another organ, or portion of the body without affecting its biological effect. Each carrier should be “acceptable” in the sense of being compatible with the other ingredients of the composition and not injurious to the subject. Novel bioactive nucleosides disclosed herein can be combined with a pharmaceutically acceptable carrier to form a more facile administrable composition. General Discussion [0031] Various embodiments may provide novel, highly efficient, and selective anti-viral agents capable of protecting against diseases, including the emerging threat of biological warfare. Without being bound by theory, it is hypothesized that the attachment of a modifying moiety at the 5-carbon of NHC may make it less recognizable to cellular targets, which will reduce incidence of the off-target effects, while keeping the 4-hydroxylamimne moiety will retain the antiviral activity shown by NHC. Identification of the new lead compound with the activity similar to that of NHC but without its mutagenicity may allow moving forward with definitive in vivo tests in mouse models, to eventually develop drugs that will protect against diseases and emerging bioweapon threats. [0032] Various embodiments relate to the synthesis of novel bioactive nucleosides and assaying their antiviral activity and cytotoxicity. Without being bound by theory, it is hypothesized that the novel base-modified nucleosides undergo cellular uptake followed by stepwise 5'-phosphorylation into active 5'-triphosphates that may interfere with viral RNA synthesis, while not affecting the host cellular targets. [0033] Further improvement of the initial hit compounds to a lead compound is also contemplated and is within the scope of the present disclosure. Without being bound by theory, it is hypothesized that attaching/removing substituents within the modifying chemical moiety, or, should the lead compound contain a chiral moiety, synthesizing two separate stereoisomers for individual examination, will allow further improvement of both potency and SI of the initial hit(s). [0034] Various embodiments may provide an NHC-based drug candidate that will retain the potency of the parent compound, but will be lacking its side effects, including cytotoxicity and mutagenicity. This result is expected to have an important positive impact by providing strong justification for continued drug development to protect against emerging bioweapon threats, particularly encephalitis viruses, as well as commonly transmitted infectious diseases, such as SARS-CoV-2 and COVID-19. [0035] Since the mutagenic properties of NHC substantially limit its potential to become a drug a need exists for new molecular structure that would result in the development of a novel anti-RNA viral lead nucleosides with an improved therapeutic potential compared to that of NHC. As described herein, a novel compound, having Structure IV, was identified. Structure IV [0036] It is to be appreciated that an anomer is a type of geometric variation found at certain atoms in carbohydrate molecules. An epimer is a stereoisomer that differs in configuration at any single stereogenic center. An anomer is an epimer at the hemiacetal/hemiketal carbon in a cyclic saccharide, an atom called the anomeric carbon. The anomeric carbon is the carbon derived from the carbonyl carbon compound (the ketone or aldehyde functional group) of the open-chain form of the carbohydrate molecule. Two anomers are designated alpha (α) or beta (β), according to the configurational relationship between the anomeric center and the anomeric reference atom, hence they are relative stereodescriptors. Structure IV may be synthesized via α- D-ribofuranose (α-D-Rb) or β-D-ribofuranose (β-D-Rb). [0037] It is to be appreciated that variations of Structure IV are contemplated and included in this disclosure. Structure V provides a more generalized structure. Structure V [0038] According to Structure V, R1 may be any substituted or unsubstituted aryl moiety. For example, R1 may be a substituted or unsubstituted phenyl moiety. The substituted aryl moiety may comprise one or more linear, branched, or cylic C1-C6 alkanes, alkenes, or alkynes. Additionally or alternatively, the substituted aryl moiety may comprise one or more halides. According to various embodiments, R1 may be a tert-butyl substituent. [0039] Still referring to Structure V, R2 may be a hydrogen, or a linear, branched, or cyclic C1-C6 alkane, alkene, or alkyne. [0040] Still referring to Structure V, R3 may be oxygen, nitrogen, an amine, or an imine, such as an oxime. [0041] Still referring to Structure V, R4 may be may be nitrogen or an imine. [0042] Still referring to Structure V, R5 may be hydrogen, or an α-D-ribofuranose (α-D-Rb) or β-D-ribofuranose (β-D-Rb) moiety. [0043] Many variations of Structure V were tested and the results are reported hereinafter in Table I. [0044] Various novel nucleoside analogs described herein have the promise of achieving higher efficiency against a variety of viral infections, including the dangerous respiratory ones, like SARS-CoV-2 and COVID-19, as well as lower incidence and diminished severity of side effects. This contribution is significant because it is expected to remove potential risk of failure that would otherwise undermine definitive investigations potentially progressing to a clinical trial. Revealing how the structural features of the proposed anti-viral species are responsible for their chemotherapeutic action will open the door for further lead optimization to discover new, more efficient anti-infectious drug candidates. Such drug candidates are expected to provide a strong framework for the continued development of novel therapies by reducing non-specific or off-target toxicities. Finally, successful completion of the proposed research is expected to yield new fundamental insights regarding optimal approaches toward nucleobase modifications for anti-viral drug development. [0045] The status quo pertaining to the current most effective nucleoside and nucleobase chemotherapeutic drugs is that these agents closely resemble natural analogs. Such resemblance gives these antimetabolites the desired anticancer or antiviral activity, but also leads to off-targeting due to metabolic and catabolic enzymatic recognition. To overcome this limitation, first, various embodiments utilize a modifying moiety that will minimize off-targeting while allowing chemotherapeutic action presumably consisting in interfering of the 5′-phosphorylated prodrug nucleosides with nucleic acid producing enzymes in viruses. Various embodiments, therefore, represent a departure from the status quo for novel ribonucleoside antimetabolites by the original design including the bulky group attached to the nucleobase, making it less structurally similar to natural pyrimidine derivatives. This is a significant improvement compared to other antimetabolites, for it is allowing the mode of action to focus on inhibiting viral replication, rather than affecting multiple intracellular targets, which is responsible for potentially severe off-target effects. [0046] The positive impact of the proposed innovations is expected to be the development of new drug candidates, which will create exciting new opportunities for the development of novel and uniquely powerful anti-viral agents to protect from the emerging threat of biological warfare as well as commonly transmitted infectious diseases like influenza, SARS-CoV-2, and COVID-19. [0047] The nucleoside compounds of the present disclosure may be used alone or in combination with other agents effective against viral infection. They may be administered separately during the course of treatment, or may be administered in combination with an additional antiviral agent, for example, in a single dosage form such as a tablet, intravenous solution or capsule. The other agents effective against viral infections include viral growth inhibitors. Viral growth inhibitors preferably used in combination with the antiviral knockdown agent of the present disclosure are reverse transcriptase inhibitors. When the virus is a hepatitis B virus, the viral growth inhibitor used in combination with the novel nucleoside compounds of the present disclosure is an HBV growth inhibitor, including in particular, interferon, peginterferon, lamivudine, adefovir, entecavir, tenofovir, telbivudine, and clevudine, among which entecavir is preferred. [0048] A nucleoside compound of the present disclosure can be administered simultaneously or sequentially with another agent, such as an antiviral, an antibiotic, an anti- inflammatory, or another agent. For example, a nucleoside compound can be administered simultaneously with another agent, such as a known antiviral, an antibiotic or an anti-inflammatory. Simultaneous administration can occur through administration of separate compositions, each containing one or more of an nucleoside compound, a known antiviral, an antibiotic, an anti-inflammatory, or another agent. Simultaneous administration can occur through administration of one composition containing two or more of a nucleoside compound, an antiviral, an antibiotic, an anti-inflammatory, or another agent. A nucleoside compound can be administered sequentially with an antiviral, an antibiotic, an anti- inflammatory, or another agent. For example, an nucleoside compound can be administered before or after administration of an antiviral, an antibiotic, an anti- inflammatory, or another agent. [0049] The present invention also includes pharmaceutical compositions and formulations of antiviral nucleosides. In typical embodiments, pharmaceutical compositions comprise therapeutically effective amounts of at least one antiviral nucleoside, which amounts treat or prevent viral infection in a subject. Pharmaceutical compositions for use in the present methods include therapeutically effective amounts of one or more antiviral nucleosides, i.e., an amount sufficient to prevent or treat the diseases described herein in a subject, formulated for local or systemic administration. There may be instances where two antiviral nucleosides of different structure are combined as one therapy in order to reach specific compartments within the subject for better therapeutic outcomes. The subject is preferably a human but can be non-human as well. A suitable subject can be an individual who is suspected of having, has been diagnosed as having, or is at risk of developing a viral infection. [0050] The duration of treatment can extend over several days or longer, depending on the condition, with the treatment continuing until the viral infection is sufficiently reduced or eliminated. Antiviral nucleosides for therapeutic administration are preferably low in toxicity. The progress of this therapy is easily monitored by conventional techniques and assays that may be used to adjust dosage to achieve a desired therapeutic effect. [0051] A composition of the antiviral nucleosides can also include a pharmaceutically acceptable carrier. Antiviral nucleosides containing compositions may contain, for example, such normally employed additives as binders, fillers, carriers, preservatives, stabilizing agents, emulsifiers, buffers and excipients as, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, cellulose, magnesium carbonate, and the like. These compositions typically contain 1%-95% of active ingredient, preferably 2%-70% active ingredient. [0052] The antiviral nucleoside can also be mixed with diluents or excipients which are compatible and physiologically tolerable as selected in accordance with the route of administration and standard pharmaceutical practice. Suitable diluents and excipients are, for example water saline dextrose glycerol or the like and combinations thereof. In addition, if desired, the compositions may contain minor amounts of auxiliary substances such as wetting or emulsifying agents, stabilizing or pH buffering agents. [0053] The formulations may also contain more than one active compound as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other. Such molecules are suitably present in combination in amounts that are effective for the purpose intended. Synthesis of novel bioactive nucleosides and assaying their antiviral activity and cytotoxicity. [0054] Synthesis of the novel ribonucleosides according to various embodiments may be preformed according to Scheme 1 commenced from commercially available 5- chloromethyluracil that was coupled to an appropriate alcohol in neat, anhydrous conditions to yield the 5-modified uracil nucleobases followed by Lewis acid mediated coupling to β-D-ribofuranose-1,2,3,5-tetraacetate and removal of the acetyl groups to yield the corresponding uridine derivatives. Sometimes, particularly in case of smaller- sized 5-substituent formation of the other anomer, namely 1-α-D-ribofuranosyl-5- substituted uracil (the α-anomer) was observed. Its ratio to the desired β-anomer, however, decreases with the increase of the R1 group from H (1:1) to isopropyl (1:5), and in case of tert-butyl or cyclohexyl the α-anomer does not form at all. Protection of the sugar OH-ends with tert-butyldimethylsilyl groups followed by O ⁴ -sulfonylation followed by reaction with ammonia or hydroxylamine yielded the immediate precursors for the cytidine and the N-hydroxycytidine derivatives, respectively, accessible by the subsequent TBS removal using tetra-n-butylammonium fluoride trihydrate.

[0055] Scheme 1 [0056] Still referring to Scheme 1, the notations (i) – (viii) have the following meanings: (i) Appropriate alcohol, neat, 120ºC; (ii) HMDS, reflux, then β-D-ribofuranose 1,2,3,5-tetraacetate, SnCl4, CH2Cl2 (anhydrous), 0ºC; (iii) NaOH, MeOH, 0ºC to room temperature; (iv) TBSCl, imidazole, CH2Cl2 (anhydrous), 0ºC to room temperature; (v) TPSCl, 4,4-Dimethylaminopyridine, diisopropylethylamine, CH2Cl2 (anhydrous), 0ºC to room temperature; (vi) Hydroxylamine hydrochloride, triethylamine, acetonitrile (anhydrous), 0ºC to room temperature; (vii) Ammonia (7 N in methanol), 1,4-dioxane (anhydrous), high pressure tube, 90ºC; (viii) tetra-n-butylammonium fluoride trihydrate, tetrahydrofuran, 0ºC to room temperature. [0057] The attempt to achieve O ⁴ -sulfonylation of the α-anomers of base- modified U-nucleosides resulted in N ³ -sulfonylation instead, as illustrated in Scheme 2. Treatment of these derivatives with either ammonia or hydroxylamine reverted them back to the starting TBS-protected compounds. [0058] Scheme 2 [0059] Still referring to Scheme 1, the notations (i) – (iv) have the following meanings: (i) TBSCl, imidazole, CH2Cl2 (anhydrous), 0ºC to room temperature; (ii) TPSCl, 4,4-Dimethylaminopyridine, diisopropylethylamine, CH2Cl2 (anhydrous), 0ºC to room temperature; (iii) Hydroxylamine hydrochloride, triethylamine, acetonitrile (anhydrous), 0ºC to room temperature; (iv) Ammonia (7 N in methanol), 1,4-dioxane (anhydrous), high pressure tube, 90ºC. [0060] The substituents vary with the size and the character, e.g., alkyl versus aryl, as well as substituted aryl versus non-substituted. Additionally, there is also a control compound with the missing alkyl substituent (i.e., 5-hydroxymethyl NHC). The proposed variation in sizes and the character of the substitution patterns is meant to attenuate the activity versus side effects, particularly cytotoxicity and mutagenicity. Evaluation of nucleoside antiviral activity and cytotoxicity in cells [0061] To evaluate the activity of the synthesized nucleoside derivatives against Venezuelan equine encephalitis virus (VEEV) that has been chosen as the model alphavirus, 3000 cells / well of MRC-5 (human lung fibroblast) were seeded in two 384 well imaging plates (35ul of Minimum Essential Medium (MEM) growth medium with 10% fetal bovine serum). After 24 hours, cells were pre-treated with the 5ul of 100um concentration of compounds or DMSO in control wells (≤ 0.5% final concentration) for 2 hours. All 29 compounds were added in 2 replicates in each plate. (4 replicates in total). The cells were then infected with Venezuelan Equine Encephalitis Virus (VEEV, 1CSH3 strain) (0.27 MOI, 10 µl.) After 16hrs post infection, cells were fixed in 10% formalin for 24 hours. The plates were then washed with Dulbecco’s phosphate buffered saline (DPBS) and then cells were permeabilized and blocked for one hour with DPBS containing 0.1% Triton X-100 and 3% BSA. To detect virus, infected cells were incubated for 1 hour with 1A4A-1 primary antibody against VEEV envelope 2 (E2) protein (1:1000 dilution in blocking buffer). After subsequent washing and incubation for 1 hr with anti-mouse Daylight 488 secondary antibody (1:2000 dilution in blocking buffer), the cells were stained with Hoechst nuclear dye 1:10,000, Invitrogen H3570, 1 µg/ml in PBS) and CellMask Deep Red dye (1:10,000, Invitrogen H32721, 5 µg/ml in PBS) for host cell cytoplasmic staining. The automated image acquisition was performed using an Opera QEHS confocal system (Perkin Elmer) and images analyzed using Acapella software. A compound that exhibits a ≥ 50% inhibition/reduction in virus infections and ≤ 20% loss in cell number in all 4 replicates is considered a hit. An internal reference inhibitor β-d-N ⁴ -Hydroxycytidine (NHC) served as a positive viral growth inhibitor control. The results of screening at 100 µM are summarized below (Table 1), in which Biological activity of modified nucleobase and base-modified nucleoside derivatives against VEEV at 100 mM: % Infection inhibition (% Cell death) ^a . Superscript ^a indicates: each experiment was performed in triplicate, the mean value and standard deviation are given. Superscript ^b indicates: Not Applicable (the compound was not produced).

Table 1

Table 1 (continued) [0062] Figure 1 is an example according to various embodiments, illustrating the bioactivity of a compound having Structure IV (RIID1271) and control (NHC) compounds. [0063] Figure 2 is an example according to various embodiments, illustrating the cytotoxicity a compound having Structure IV (RIID1271) and control (NHC) compounds. [0064] The anti-infection activity of the 5-modified nucleobases was diminutive, as was that of nucleoside derivatives with substituents of a smaller size. Nucleosides with larger R1 and R2 inhibited the infection at a higher rate, but the only compound with outstanding activity was RIID#1271 that showed almost complete suppression of the VEEV infection in the living cells. This derivative showed almost complete suppression of the VEEV infection in the living cells at 100 µM. This promising result warranted a more detailed insight in the activity of RIID1271, such as determination of efficiency (EC50) and cytotoxicity (CC50) (Figure 2), and comparison of these parameters to those of the parent NHC (Table 2). Table 2: Inhibition of the VEEV infection (EC50) and cytotoxicity (CC50) for RIID1271 and NHC ^a . Superscript ^a indicates that each experiment was determined in triplicate, the mean value and standard deviation are given. Superscript ^b indicates Safety Index = CC50/EC50. It is based on short term effects (i.e., cell death) only; long term effects do not factor in. [0065] Table 2 [0066] [0067] The new lead compound does not outperform the current bioactive compound, NHC, in terms of activity, but the latter is a mutagen.

EXAMPLES Introduction [0068] The following examples are put forth to provide those of ordinary skill in the art with a complete disclosure and description of how to perform the methods, how to make, and how to use the compositions and compounds disclosed and claimed herein. Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.), but some errors and deviations should be accounted for. The purpose of the following examples is not to limit the scope of the various embodiments, but merely to provide examples illustrating specific embodiments. [0069] All chemicals, reagents, and solvents were purchased from Sigma-Aldrich Inc., Alfa Aesar, Cambridge Isotope Laboratories, and Fisher Scientific, Inc, and used as received unless stated otherwise. All reactions were carried out under the atmosphere of dry nitrogen in oven-dried glassware. Indicated reaction temperatures refer to those of the reaction bath, while room temperature (r.t.) is noted as 25°C. Pure reaction products were typically dried under high vacuum in the presence of phosphorus pentoxide. Analytical thin layer chromatography (TLC) was performed with glass backed silica plates (5 x 20 cm, 60 Å, 250 μm). Visualization was accomplished using a 254 nm UV lamp. ¹ H and ¹³ C NMR spectra of synthesized compounds dissolved in either chloroform-d or methanol-d4 were recorded on either a Bruker Avance 400 MHz spectrometer or Bruker DPX 500 MHz. Chemical shifts are reported in ppm with multiplicity (singlet, d = doublet, dd = doublet of doublet, t = triplet, q = quartet, b = broad, m = multiplet), number of protons, and coupling constants. High resolution mass spectral data were collected on Shimadzu Q-TOF 6500 or Bruker SolariX XR FT-ICR-MS. Melting points were determined on Mel-Temp Electrothermal. Examples 1 – 12: Synthesis of 5-modified uracils [0070] General procedure for the synthesis of 5-modified uracils was as follows and as illustrated in the following reaction scheme. 5-Chloromethyluracil and an appropriate alcohol (4-11 eq.) were heated neat at the temperature ranging from +120 to +135ºC for the period of time ranging from 2.5 to 5 h under nitrogen atmosphere. The mixture was cooled down to room temperature, dissolved in dichloromethane/methanol=20:1, and silica (ca 5 g) was added. The solvent was removed under reduced pressure and the solid was applied onto a silica gel column primed with dichloromethane. Chromatography (SiO2, CH2Cl2/MeOH eluting from 1:0 to 20:1) afforded the product as a fine white powder. [0071] Example 1: 5-[1-phenyl-2,2-(dimethyl)propoxymethyl]uracil [0072] 5-[1-phenyl-2,2-(dimethyl)propoxymethyl]uracil (VAL-1-75 – RIID1255) was prepared by the following procedure and with the following results: Treatment of 5- chloromethyluracil (322 mg, 2.000 mmol) with 2,2-dimethyl-1-phenyl-1-propanol (1.32 g, 8.000 mmol) at 135 ºC for 3 hours afforded after purification 476 mg of product (83%). ¹ H NMR (400 MHz, Methanol-d4) δ 7.30 (m, 6 H), 4.07 (m, 2 H), 3.97 (AB d, 1 H, J = 12.4 Hz), 0.89 (s, 9 H). ¹³ C NMR (100 MHz, CD3OD) δ 165.97 (C), 153.42 (C), 140.84 (C), 140.73 (CH), 129.58 (CH), 128.62 (CH), 128.44 (CH), 112.14 (C), 91.04 (CH), 64.72 (CH2), 36.51 (C), 26.75 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C16H21N2O3 calculated: 289.15467, observed: 289.15465; for [MNa] ⁺ C16H20N2O3Na calculated: 311.13661, observed: 311.13661. M.P.263 - 264 ºC. Example 2: 5-[1-(2-methyl)phenyl-2,2-(dimethyl)propoxymethyl]uracil [0073] 5-[1-(2-methyl)phenyl-2,2-(dimethyl)propoxymethyl]uracil (SKR-1-28 – VAL-1-90F1 – RIID1167) was prepared by the following procedure and with the following results: Treatment of 5-chloromethyluracil (110 mg, 0.680 mmol) with 2,2- dimethyl-1-(2-methylphenyl)-1-propanol (487 mg, 2.730 mmol) at 120 ºC for 5 hours afforded after purification 150 mg of product (73%). ¹ H NMR (400 MHz, Methanol-d4) δ 7.37 (m, 1 H), 7.29 (s, 1 H), 7.15 (m, 3 H), 4.44 (s, 1 H), 3.97 (s, 2 H), 2.35 (s, 3 H), 0.94 (s, 9 H). ¹³ C NMR (100 MHz, CD3OD) δ 165.94 (C), 153.40 (C), 140.70 (CH), 139.12 (C), 138.20 (C), 131.22 (CH), 129.04 (CH), 128.16 (CH), 126.34 (CH), 112.20 (C), 85.13 (CH), 64.45 (CH2), 37.77 (C), 26.80 (CH3), 20.52 (CH3). HRMS (ESI ⁺ ) for [MNa] ⁺ C17H22N2O3Na calculated: 325.15281, observed: 325.15225. M.P.266 - 267 ºC. Example 3: 5-[1-(2-chloro)phenyl-2,2-(dimethyl)propoxymethyl]uracil [0074] 5-[1-(2-chloro)phenyl-2,2-(dimethyl)propoxymethyl]uracil (SKR-1-3 – VAL- 1-98 – RIID1152 was prepared by the following procedure and with the following results: Treatment of 5-chloromethyluracil (205 mg, 1.280 mmol) with 2,2-dimethyl-1-(2- chloro)phenyl-1-propanol (1.017 g, 5.120 mmol) at 128 ºC for 3.5 hours afforded after purification 53 mg of product (26%). ¹ H NMR (400 MHz, Methanol-d4) δ 7.48 (m, 1 H), 7.35 (m, 1 H), 7.26 (m, 3 H), 4.64 (s, 1 H), 4.04 (AB d, 1 H, J = 12.2 Hz), 3.99 (AB d, 1 H, J = 12.2 Hz), 0.95 (s, 9 H). ¹³ C NMR (100 MHz, CD3OD) δ 165.87 (C), 153.38 (C), 141.32 (CH), 138.81 (C), 135.71 (C), 131.08 (CH), 130.26 (CH), 129.81 (CH), 127.57 (CH), 111.51 (C), 84.77 (CH), 65.13 (CH2), 37.72 (C), 26.51 (CH3). HRMS (ESI-) for [M- H]- C16H18ClN2O3 calculated: 321.10114, observed: 321.10176. M.P.248 - 249 ºC. Example 4: 5-[1-phenyl-1-(cyclohexyl)methoxymethyl]uracil [0075] 5-[1-phenyl-1-(cyclohexyl)methoxymethyl]uracil (SKR-1-1 – SSS-1-3 – RIID1127 was prepared by the following procedure and with the following results: Treatment of 5-chloromethyluracil (153 mg, 0.951 mmol) with 1-(phenyl)cyclohexanol (724 mg, 3.805 mmol) at 126 ºC for 2.5 hours afforded after purification 182 mg of product (61%). ¹ H NMR (400 MHz, Methanol-d4) δ 7.31 (m, 3 H), 7.25 (s, 3 H), 7.29 (m, 3 H), 4.05 (m, 2 H), 3.99 (m, 1 H), 2.05 (m, 1 H), 1.73 (m, 1 H), 1.63 (m, 3 H), 1.27 (m, 4 H), 1.05 (m, 1 H), 0.92 (m, 1 H). ¹³ C NMR (100 MHz, CD3OD) δ 165.98 (C), 153.41 (C), 142.31 (C), 141.04 (CH), 129.21 (CH), 128.60 (CH), 112.01 (C), 88.29 (CH), 64.32 (CH2), 45.75 (CH), 30.65 (CH2), 30.45 (CH2), 27.65 (CH2), 27.18 (CH2), 27.13 (CH2). HRMS (ESI-) for [M-H]- C18H21N2O3 calculated: 313.15577, observed: 313.15634. M.P. 237 - 239 ºC. Example 5: 5-[1-(phenyl)heptoxymethyl]uracil [0076] 5-[1-(phenyl)heptoxymethyl]uracil (SKR-1-32 – RIID1134 was prepared by the following procedure and with the following results: Treatment of 5-chloromethyluracil (75 mg, 0.460 mmol) with 1-phenyl-1-heptanol (199 mg, 1.860 mmol) at 135 ºC for 3 hours afforded after purification 24 mg of product (16%). ¹ H NMR (400 MHz, Methanol- d4) δ 7.26 (m, 6 H), 4.35 (t, 1 H, J = 6.1 Hz), 4.05 (m, 2 H), 2.09 (m, 2 H), 1.81 (m, 1 H), 1.66 (m, 1 H), 1.35 (m, 6 H), 0.87 (m, 3 H). ¹³ C NMR (100 MHz, CD3OD) δ 166.01 (C), 153.42 (C), 143.81 (C), 141.25 (CH), 129.46 (CH), 128.62 (CH), 128.81 (CH), 111.91 (C), 83.55 (CH), 64.13 (CH2), 39.30 (CH2), 32.95 (CH2), 30.27 (CH2), 26.82 (CH2), 23.63 (CH2), 14.38 (CH3). HRMS (ESI ⁺ ) for [MNa] ⁺ C18H24N2O3 calculated: 339.16791, observed: 339.16794. Example 6: 5-[1-(phenyl)ethoxymethyl]uracil [0077] 5-[1-(phenyl)ethoxymethyl]uracil (VAL-1-142 – VAL-1-149 – RIID1129) Treatment of 5-chloromethyluracil (505 mg, 3.145 mmol) with 1-phenyl-1-ethanol (1537 mg, 12.581 mmol) at 120 ºC for 4 hours afforded after purification 551 mg of product (71%). ¹ H NMR (400 MHz, Methanol-d4) δ 7.34 (m, 5 H), 7.27 (m, 1 H), 4.55 (q, 1 H, J = 6.5 Hz), 4.10 (AB dd, 1 H, J = 12.1, 0.9 Hz), 4.06 (AB dd, 1 H, J = 12.1, 1.0 Hz), 1.43 (d, 1 H, J = 6.5 Hz). ¹³ C NMR (100 MHz, CD3OD) δ 166.03 (C), 156.50 (C), 144.82 (C), 141.29 (CH), 129.54 (CH), 128.63 (CH), 127.28 (CH), 111.85 (C), 79.42 (CH), 64.08 (CH2), 24.36 (CH3). HRMS (ESI-) for [M-H] ⁺ C13H13N2O3 calculated: 245.09312, observed: 245.09317. M.P.244 - 245 ºC (lit. ¹ 234-235 ºC). Example 7: 5-[1-(phenyl)propoxymethyl]uracil [0078] 5-[1-(phenyl)propoxymethyl]uracil (VAL-2-3 – RIID1361 was prepared by the following procedure and with the following results: Treatment of 5-chloromethyluracil (522 mg, 3.251 mmol) with 1-phenyl-1-propanol (3542 mg, 26.009 mmol) at 125 ºC for 16 hours afforded after purification 657 mg of product (78%). ¹ H NMR (400 MHz, Methanol-d4) δ 7.30 (m, 6 H), 4.28 (t, 1 H, J = 6.6 Hz), 4.07 (s, 2 H), 1.83 (m, 1 H), 1.66 (m, 1 H), 0.88 (t, 3 H, J = 7.5 Hz). ¹³ C NMR (100 MHz, CD3OD) δ 166.00 (C), 153.42 (C), 143.52 (C), 141.20 (CH), 129.43 (CH), 128.65 (CH), 127.87 (CH), 111.93 (C), 85.10 (CH), 64.20 (CH2), 32.09 (CH2), 30.27 (CH2), 10.54 (CH3). HRMS (ESI-) for [MH] ⁺ calculated: 261.12892, observed: 261.13095. M.P.227 - 228 ºC. Example 8: 5-[(1-phenyl-2-methyl)propoxymethyl]uracil [0079] 5-[(1-phenyl-2-methyl)propoxymethyl]uracil (VAL-2-33 – RIID1133 was prepared by the following procedure and with the following results: Treatment of 5- chloromethyluracil (500 mg, 3.114 mmol) with 1-phenyl-2-methyl-1-propanol (2480 mg, 16.509 mmol) at 124 ºC for 21 hours afforded after purification 547 mg of product (64%). ¹ H NMR (400 MHz, Methanol-d4) δ 7.28 (m, 6 H), 4.03 (m, 3 H), 1.83 (m, 1 H), 1.90 (m, 1 H), 1.00 (d, 3 H, J = 6.6 Hz), 0.73 (d, 3 H, J = 6.8 Hz). ¹³ C NMR (100 MHz, CD3OD) δ 165.98 (C), 153.42 (C), 142.40 (C), 141.03 (CH), 129.21 (CH), 128.61 (CH), 128.58 (CH), 112.02 (C), 89.15 (CH), 64.39 (CH2), 36.05 (CH), 19.38 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ calculated: 275.13902, observed: 275.13909; for [MNa] ⁺ calculated: 297.12096, observed: 297.12102. M.P.243 - 244 ºC. Example 9: 5-[benzyloxymethyl]uracil [0080] 5-[benzyloxymethyl]uracil (VAL-1-110 – VAL-1-114 – RIID1273 was prepared by the following procedure and with the following results: Treatment of 5- [0001] 1 Abdel-Megied, A. E. S., Motawia, M. S., Pedersen, E. B., Nielsen, C. M. 5-Alkoxymethyl-1-hydroxyalkyluracils with potential anti-HIV activity Heterocycles 1992, 34 713-722 DOI: 103987/COM-91-5888 chloromethyluracil (321 mg, 2.000 mmol) with benzyl alcohol (865 mg, 8.000 mmol) at 135 ºC for 4.5 hours afforded after purification 238 mg of product (41%). ¹ H NMR (400 MHz, Methanol-d4) δ 7.33 (m, 6 H), 4.57 (s, 2 H), 4.27 (s, 2 H). ¹³ C NMR (100 MHz, CD3OD) δ 166.27 (C), 153.47 (C), 141.84 (C), 139.50 (CH), 129.40 (CH), 128.96 (CH), 128.75 (CH), 111.49 (C), 73.68 (CH2), 65.58 (CH2). M.P.214 - 216 ºC (lit.2196 - 198 ºC). Example 10: 5-[({2-chloro}benzyloxy)methyl]uracil [0081] 5-[({2-chloro}benzyloxy)methyl]uracil (VAL-2-18 – RIID1379). Treatment of 5-chloromethyluracil (0.804 g, 5.01 mmol) with 2-(chloro)benzyl alcohol (7.140 g, 50.10 mmol) at 126 ºC for 30 hours afforded after purification 772 mg of product (58%). ¹ H NMR (400 MHz, Methanol-d4) δ 7.53 (m, 1 H), 7.47 (s, 1 H), 7.38 (m, 1 H), 7.27 (m, 2 H), 4.67 (s, 2 H), 4.33 (s, 2 H). ¹³ C NMR (100 MHz, CD3OD) δ 166.14 (C), 153.44 (C), 142.02 (CH), 137.09 (C), 134.18 (C), 130.73 (CH), 130.32 (CH), 130.15 (CH), 128.05 (CH), 111.33 (C), 70.58 (CH2), 66.00 (CH2). HRMS (ESI-) for [MH] ⁺ C12H11 ³⁵ ClN2O3 calculated: 267.05364, observed: 267.05650. M.P.218 - 220 ºC. Example 11: 5-[methoxymethyl]uracil [0082] 5-[methoxymethyl]uracil (VAL-2-46 - RIID1385) was prepared exactly as described previously.3 ¹ H NMR (400 MHz, Methanol-d4) δ 7.42 (s, 1 H), 4.14 (s, 2 H), 3.36 (s, 3 H). ¹³ C NMR (100 MHz, CD3OD) δ 166.14 (C), 153.43 (C), 141.96 (CH), 111.22 (C), 67.67 (CH2), 58.40 (CH3). Example 12: 5-[hydroxymethyl]uracil [0083] 5-[hydroxymethyl]uracil (RIID1301) was purchased from Sigma-Aldrich (catalog #852589). [0001] 2 Farkas, J., Sorm, F. Nucleic acid components and their analogs. CXXV. Synthesis of 5-[bis(2- chloroethyl)aminomethyl]uridine hydrochloride. Coll. Czech. Chem. Commun.1969, 34, 1696-1701. DOI:10.1135/cccc19691696 3 Brulikova, L., Dzubak, P., Hajduch, M., Hlavac, J. Synthesis of various 5-alkoxymethyluracil analogs and structure-cytotoxic activity relationship study. Carbohydrate Res.2011, 346, 2136-2144. DOI: 10.1016/j.carres.2011.07.026 Examples 13 – 23: synthesis of 5-modified-2′,3′,5′-tris-O-triacetyluridines and synthesis of 5-modified-uridines [0084] General procedure for the synthesis of 5-modified-2′,3′,5′-tris-O- triacetyluridines. A 5- modified uracil was dispersed in hexamethyldisilazane (75-200 eq) followed by addition of ammonium sulfate (0.3 eq.). The reaction mixture was heated at reflux under nitrogen atmosphere for the period from 1 to 3 h, until a clear solution formed, then cooled down, and the excess of hexamethyldisilazane was removed under reduced pressure. The residue was dissolved in anhydrous dichloromethane to the concentration of about 25 mM followed by addition of β-D- ribofuranose-1,2,3,5-tetraacetate (1.1 eq.). The solution was immersed into ice-water bath and stirred for 10 min followed by addition of tin(IV) chloride (1.1 eq.). The reaction mixture was stirred at the temperature ranging from 0 to +5 ºC for the period from 3 to 6 h, then poured into an equal volume of saturated aqueous solution of NaHCO3. The organic layer was separated, and the aqueous layer was extracted thrice with an equal amount of dichloromethane. Combined organic extracts were washed with equal volume of water, brine, and dried over anhydrous Na2SO4. The solvent was evaporated, and the residue was applied onto a chromatography column (SiO2, Hexanes/ EtOAc eluting from 4:1 to 1:1) to afford a crude caramel-like mixture consisting of the target product and, occasionally, starting materials (modified 5-uracils and -D-ribofuranose-1,2,3,5-tetraacetate) that were introduced into the subsequent transformation without characterization and further purification. [0085] General procedure for the synthesis of 5-modified-uridines. Crude 5- modified 2′,3′,5′-triacetyluridine was dissolved in methanol (to ca 20 mM based on the amount of the starting material in the previous procedure) and immersed into ice-water bath for 10 min. A solution of sodium hydroxide (1 M in MeOH, 5.0 eq) was added. The reaction mixture was stirred for the period randing from 5 to 24 h while gradually warming up to room temperature. The solution was re-immersed into ice-water bath, and a solution of HCl (ca 1.2 M in MeOH) was added dropwise to adjust the pH to ca 2.0. The solvent was removed under reduced pressure, and the residue was applied onto a silica gel column primed with dichloromethane. Chromatography (SiO2, CH2Cl2/MeOH eluting from 1:0 to 10:1) afforded 5-modified uridine as a glass-like solid and, occasionally, its α-D-ribofuranosyl anomer (the α-anomer) as a glass-like solids and the starting 5-midified uracil as a white powder. Example 13 [0086] 5-[1-phenyl-2,2-(dimethyl)propoxymethyl]uridine (VAL-1-77 – RIID1256 was prepared by the following procedure and with the following results: Treatment of 5- [1-phenyl-2,2-(dimethyl)propoxymethyl] uracil (444 mg, 1.540 mmol) afforded after two steps 241 mg of product (65%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.94 and 7.93 (2 s, 1 H), 7.27 (m, 5 H), 5.90 and 5.89 (2 d, 1 H, J = 4.2 Hz), 4.16 (m, 2 H), 4.02 (m, 4 H), 3.84 (m, 1 H), 3.75 (m, 1 H), 0.89 (s, 9 H). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 165.00 (C), 152.39 (C), 140.91 and 140.80 (C), 140.57 and 140.37 (CH), 129.66 and 129.62 (CH), 128.62 (CH), 128.34 and 128.32 (CH), 113.12 and 113.07 (C), 91.14 and 90.97 (CH), 90.68 and 90.64 (CH), 86.40 and 86.31 (CH), 75.73 and 75.69 (CH), 71.51 and 71.36 (CH), 65.20 and 64.93 (CH2), 65.46 and 62.36 (CH2), 36.50 and 36.48 (C), 26.78 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C21H29N2O7 calculated: 421.19748, observed: 421.20261. Example 14 [0087] Example 5-[1-(2-methyl)phenyl-2,2-(dimethyl)propoxymethyl]uridine (SKR- 1-31 – VAL-1-90F2 – VAL-1-92F2 – RIID1168 was prepared by the following procedure and with the following results: Treatment of 5-[1-(2-methyl)phenyl-2,2- (dimethyl)propoxymethyl]uracil (112 mg, 0.372 mmol) afforded after two steps 45 mg of product (28%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.90 and 7.89 (2 s, 1 H); 7.40 (br m, 1 H), 7.13 (m, 3 H), 5.91 and 5.89 (2 d, 1 H, J = 4.7 and 4.4 Hz), 4.43 (s, 1 H), 4.15 (m, 2 H), 3.99 (m, 3 H), 3.83 (m, 1 H), 3.74 (AB dd, 1 H, 1 H, J = 12.1, 3.3 Hz), 2.36 and 2.35 (2 s, 3 H), 0.93 (s, 9 H). ¹³ C NMR (100 MHz, methanol-d ₄ ) for 1:1 mixture of diastereomers δ 164.95 (C), 152.42 and 152.38 (C), 140.24 and 140.22 (CH), 139.34 and 139.14 (C), 138.31 and 138.15 (C), 131.19 (CH), 129.22 (CH), 128.12 and 128.05 (CH), 126.37 and 126.31 (CH), 113.29 (C), 90.61 (CH), 86.42 (CH), 85.20 (br CH), 75.68 and 75.64 (CH), 71.56 and 71.53 (CH), 64.86 and 64.60 (CH2), 62.51 and 62.48 (CH2), 37.78 and 37.74 (C), 26.82 (CH3), 20.64 (CH3). HRMS (ESI ⁺ ) for [MNa] ⁺ C22H30N2NaO7 calculated: 457.19507, observed: 457.19454. Starting material retrieved: 26 mg (23%). Example 15 [0088] 5-[1-(2-chloro)phenyl-2,2-(dimethyl)propoxymethyl]uridine (SKR-1-27 – VAL-1-101F2 – VAL-1-103F2 – RIID1166 was prepared by the following procedure and with the following results: Treatment of 5-[1-(2-chloro)phenyl-2,2- (dimethyl)propoxymethyl]uracil (57 mg, 0.177 mmol) afforded after two steps 45 mg of product (56%). ¹ H NMR (400 MHz, CD3OD) for 1:1 mixture of diastereomers δ 7.93 and 7.91 (2 s, 1 H); 7.50 (m, 1 H), 7.31 (m, 3 H), 5.91 and 5.89 (2 d, 1 H, J = 4.3 and 5.0 Hz), 4.67 (s, 1 H), 4.19 (m, 2 H), 4.00 (m, 3 H), 3.81 (m, 1 H), 3.74 (m, 1 H), 0.95 and 0.94 (2 s, 9 H). ¹³ C NMR (100 MHz, methanol-d ₄ ) for 1:1 mixture of diastereomers δ 165.20 and 164.96 (C), 151.12 (C), 140.87 and 140.51 (C), 139.39 and 139.07 (CH), 135.71 (C), 131.07 (CH), 130.26 (CH), 129.80 (CH), 127.57 (CH), 112.93 and 122.72 (C), 90.61 (CH), 86.57 and 86.13 (CH), 84.21 and 84.15 (CH), 75.69 (CH), 71.54 (CH), 65.13 and 64.95 (CH2), 62.45 (CH2), 37.71 (C), 26.54 (CH3). HRMS (ESI ⁺ ) for [MNa] ⁺ C21H27 ³⁵ ClN2NaO7 calculated: 477.14045, observed: 477.13990. Starting material retrieved: 18 mg (32%). Example 16 [0089] 5-[1-phenyl-1-(cyclohexyl)methoxymethyl]uridine (SKR-1-21 – SSS-1-5 – RIID1126 was prepared by the following procedure and with the following results: Treatment of 5-[1-phenyl-1-(cyclohexyl)methoxymethyl]uracil (100 mg, 0.311 mmol) afforded after two steps 62 mg of product (54%). ¹ H NMR (400 MHz, CD3OD) for 1:1 mixture of diastereomers δ 7.94 and 7.93 (2 s, 1 H), 7.30 (m, 5 H), 5.91 (m, 1 H), 4.18 (m, 2 H), 4.03 (m, 4 H), 3.82 (m, 1 H), 3.77 (m, 1 H), 2.04 (m, 1 H), 1.73 (m, 1 H), 1.61 (m, 3 H), 1.26 (m, 2 H), 1.16 (m, 1 H), 0.08 (m, 2 H). ¹³ C NMR (100 MHz, methanol-d ₄ ) for 1:1 mixture of diastereomers δ 165.50 (C), 153.00 (C), 142.38 and 142.31 (C), 140.48 and 140.54 (C), 129.18 (CH), 128.65 (CH) and 128.62, 128.51 (CH), 113.03 (C), 90.66 and 90.59 (CH), 88.24 and 88.15 (CH), 86.57 and 86.49 (CH), 75.70 and 75.67 (CH), 71.56 and 71.43 (CH), 64.70 and 64.54 (CH2), 62.53 and 62.45 (CH2), 45.71 and 45.67 (CH), 30.64 (CH2), 30.41 (CH2), 27.64 (CH2), 27.16 (CH2), 27.11 (CH2). HRMS (ESI-) for [MNa] ⁺ C23H30N2NaO7 calculated: 469.19507, observed: 469.19405. Example 17 [0090] 5-[1-(phenyl)ethoxymethyl]uridine (SKR-1-24F1 – VAL-1-146 – RIID1128 was prepared by the following procedure and with the following results: Treatment of 5- [1-(phenyl)ethoxymethyl] uracil (551 mg, 2.239 mmol) afforded after two steps 117 mg of product (14%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 8.01 and 7.99 (2 s, 1 H); 7.34 (m, 4 H), 7.26 (m, 1 H), 5.91 and 5.88 (2 d, 1 H, J = 4.2 and 3.8 Hz), 4.55 (q, 1 H, J = 6.4 Hz), 4.16 (m, 2 H), 4.10 (m, 2 H), 4.01 (m, 1 H), 3.85 (m, 1 H), 3.74 (m, 1 H), 1.43 and 1.42 (2 d, 3 H, J = 6.4 Hz). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 162.02 (C), 152.40 (C), 144.91 and 144.83 (C), 140.83 and 140.79 (CH), 129.54 (CH), 128.59 and 128.56 (CH), 127.34 and 127.30 (CH), 112.79 and 112.75 (C), 90.79 and 90.70 (CH), 86.36 and 86.31 (CH), 79.47 and 79.37 (CH), 75.77 and 75.74 (CH), 71.38 and 71.27 (CH), 64.38 and 64.22 (CH2), 62.33 and 62.24 (CH2), 24.48 and 24.39 (CH3). HRMS (ESI ⁺ ) for [MNa] ⁺ C18H22N2NaO7 calculated: 401.13247, observed: 401.13146. The α-anomer, 1-α-D-ribofuranosyl-5-[1- (phenyl)ethoxymethyl]uracil (VAL-1-148 – RIID1130) obtained: 83 mg (10%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.33 (m, 5 H), 7.26 (m, 1 H), 6.31 (d, 1 H, J = 3.7 Hz), 4.63 (m, 2 H), 4.55 (q, 1 H, J = 6.5 Hz), 4.35 (t, 1 H, J = 6.2 Hz), 4.09 (m, 2 H), 3.89 (m, 1 H), 3.80 (AB dd, 1 H, J = 11.9, 2.9 Hz), 3.66 (AB dd, 1 H, J = 11.9, 5.6 Hz), 1.42 (d, 3 H, J = 6.5 Hz). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 164.70 (C), 152.71 (C), 144.81 (C), 140.04 (CH), 129.55 (CH), 128.64 (CH), 127.34 and 127.27 (CH), 111.60 (C), 89.63 (CH), 86.00 (CH), 79.45 (CH), 72.93 (CH), 71.67 (CH), 64.54 and 64.51 (CH2), 63.91 (CH2), 24.35 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C18H23N2O7 calculated: 379.15053, observed: 379.15544. Example 18 [0091] 5-[1-(phenyl)propoxymethyl]uridine (VAL-2-6F1 – VAL-2-11 – RIID1375 was prepared by the following procedure and with the following results: Treatment of 5- [1-(phenyl)propoxymethyl] uracil (648 mg, 2.488 mmol) afforded after two steps 298 mg of product (41%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.99 and 7.98 (2 s, 1 H); 7.34 (m, 4 H), 7.26 (m, 1 H), 5.90 (m, 1 H), 4.55 (t, 1 H, J = 6.6 Hz), 4.16 (m, 2 H), 4.06 (m, 3 H), 3.84 (m, 1 H), 3.85 (m, 1 H), 3.73 (m, 1 H), 1.82 (m, 1 H), 1.66 (m, 2 H), 0.86 (m, 3 H). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 165.04 (C), 152.39 (C), 143.51 (C), 140.80 (CH), 129.42 (CH), 128.60 (CH), 127.95 and 127.90 (CH), 112.86 (C), 90.76 and 90.68 (CH), 86.37 and 86.31 (CH), 85.16 and 85.05 (CH), 75.74 (CH), 71.41 and 71.29 (CH), 64.55 and 64.37 (CH2), 62.37 and 62.27 (CH2), 32.14 and 32.03 (CH2), 10.54 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C19H25N2O7 calculated: 393.16618, observed: 393.17110. The α-anomer, 1-α-D- ribofuranosyl-5-[1-(phenyl)propoxymethyl]uracil (VAL-2-6F2 – VAL-2-12 – RIID1376) obtained: 81 mg (11%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.26 (m, 6 H), 6.31 and 6.30 (2 d, 1 H, J = 3.7 Hz), 4.63 (m, 2 H), 4.35 (t, 1 H, J = 6.2 Hz), 4.28 (t, 1 H, J = 6.6 Hz), 4.07 (s, 2 H), 3.89 (m, 1 H), 3.80 (AB dd, 1 H, J = 11.9, 2.8 Hz), 3.66 (AB dd, 1 H, J = 11.9, 5.6 Hz), 1.85 (m, 1 H), 1.66 (m, 1 H), 0.87 (t, 3 H, J = 7.4 Hz). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 164.66 (C), 152.73 (C), 143.49 (C), 139.96 (CH), 129.44 (CH), 128.66 (CH), 127.85 (CH), 111.68 and 111.65 (C), 89.62 (CH), 85.99 (CH), 85.94 and 85.13 (CH), 72.95 (CH), 71.67 (CH), 64.68 and 64.65 (CH2), 63.92 (CH2), 32.06 (CH2), 10.55 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C19H25N2O7 calculated: 393.16618, observed: 393.17109. Example 19 [0092] 5-[1-(phenyl)heptoxymethyl]uridine (SKR-1-35 – RIID1169 was prepared by the following procedure and with the following results: Treatment of 5-[1- (phenyl)heptoxymethyl]uracil (20 mg, 0.063 mmol) afforded after two steps 3 mg of product (8%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.50 and 7.48 (2 s, 2 H), 7.36 (m, 5 H), 5.59 (m, 1 H), 5.12 (m, 1 H), 4.61 (m, 1 H), 4.31 (m, 1 H), 4.05 (m, 1 H), 4.00 (m, 2 H), 3.89 (m, 1 H), 3.78 (m, 1 H), 1.89 (m, 4 H), 1.55 (m, 5 H), 0.87 (m, 4 H). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 165.33 (C), 150.87 and 150.04 (C), 141.01 and 140.95 (CH), 139.66 (C), 129.46 (CH), 128.40 (CH), 127.81 (CH), 112.97 (C), 97.07 (CH), 88.30 and 87.60 (CH), 72.92 (CH), 73.20 (CH), 70.14 (CH), 64.28 (CH2), 61.63 and 61.29 (CH2), 38.99 (CH2), 32.64 (CH2), 30.12 (CH2), 26.52 (CH2), 23.34 (CH2), 14.10 (CH3). HRMS (ESI ⁺ ) for [MNa] ⁺ C23H32N2O7Na calculated: 471.21072, observed: 471.21023. Starting material retrieved: 6 mg (30%). Example 20 [0093] 5-[(1-phenyl-2-methyl)propoxymethyl]uridine (VAL-2-35F1 – VAL-2-39 – RIID1386 was prepared by the following procedure and with the following results: Treatment of 5-[1-(phenyl)propoxymethyl] uracil (1016 mg, 1.714 mmol) afforded after two steps 314 mg of product (45%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.96 and 7.95 (2 s, 1 H); 7.29 (m, 5 H), 5.89 (m, 1 H), 4.15 (m, 2 H), 4.07 (m, 1 H), 4.01 (m, 3 H), 3.83 (m, 1 H), 3.76 (m, 1 H), 1.92 (m, 1 H), 0.99 (d, 3 H, 1 H, J = 6.6 Hz), 0.72 (m, 3 H). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 165.00 (C), 152.39 (C), 142.49 and 142.40 (C), 140.71 and 140.60 (CH), 129.18 (CH), 128.66 and 128.62 (CH), 128.54 and 128.52 (CH), 112.97 (C), 90.71 and 90.66 (CH), 89.17 and 89.07 (CH), 86.39 and 86.32 (CH), 75.72 (CH), 71.46 and 71.34 (CH), 64.77 and 64.59 (CH2), 62.42 and 62.33 (CH2), 36.04 and 35.98 (CH), 19.46 and 19.42 (CH3) , 19.36 and 19.35 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C20H27N2O7 calculated: 407.19183, observed: 407.19819. The α-anomer, 1-α-D-ribofuranosyl-5- [(1-phenyl-2-methyl)propoxymethyl]uracil (VAL-2-35F2 – VAL-2-40 – RIID1387) obtained: 70 mg (10%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.30 (m, 6 H), 6.30 and 6.29 (2 d, 1 H, J = 3.8 Hz), 4.62 (m, 1 H), 4.35 (t, 1 H, J = 6.3 Hz), 4.05 (AB d, 1 H, J = 12.4 Hz), 4.01 (m, 2 H), 3.88 (m, 1 H), 3.80 (AB dd, 1 H, J = 11.9, 2.8 Hz), 3.66 (AB dd, 1 H, J = 11.9, 5.5 Hz), 1.91 (m, 1 H), 1.00 (d, 3 H, J = 6.6 Hz, 1 H), 0.72 (d, 3 H, J = 6.8 Hz). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 164.62 (C), 152.73 (C), 142.35 (C), 139.80 (CH), 129.21 (CH), 128.61 (CH), 128.55 (CH), 111.79 and 111.74 (C), 89.61 (CH), 89.23 and 89.18 (CH), 85.99 (CH), 72.96 (CH), 71.67 (CH), 64.88 and 64.86 (CH2), 63.92 (CH2), 36.02 (CH2), 19.40 (CH3) , 19.37 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C20H27N2O7 calculated: 407.19183, observed: 407.19144. Example 21 [0094] 5-[(benzyloxy)methyl]uridine (VAL-1-116 – VAL-1-120 – RIID1284).4 Treatment of 5-[(benzyloxy)methyl]uracil (238 mg, 0.826 mmol) afforded after two steps 100 mg of product (35%). ¹ H NMR (400 MHz, Methanol-d4) δ 8.10 (s, 1 H), 7.31 (m, 5 H), 5.90 (d, 1 H, J = 4.2 Hz), 4.56 (s, 2 H), 4.30 (AB dd, 1 H, J = 11.9, 0.5 Hz), 4.25 (AB dd, 1 H, J = 11.9, 0.6 Hz), 4.17 (m, 2 H), 4.01 (m, 1 H), 3.85 (AB dd, 1 H, J = 12.2, 2.7 Hz), 3.74 (AB dd, 1 H, J = 12.2, 3.1 Hz). ¹³ C NMR (100 MHz, CD3OD) δ 165.17 (C), 153.04 (C), 141.42 (CH), 139.51 (C), 129.40 (CH), 129.95 (CH), 128.72 (CH), 112.31 (C), 97.79 (CH), 86.32 (CH), 75.75 (CH), 73.59 (CH2), 71.23 (CH), 65.80 (CH2), 62.23 (CH2). HRMS (ESI ⁺ ) for [MH] ⁺ C17H21N2O7 calculated: 365.13488, observed: 365.14053. The α-anomer, 1-α-D-ribofuranosyl-5-[(benzyloxy)methyl]uracil (VAL-1-130 – RIID1289) obtained: 108 mg (36%). ¹ H NMR (400 MHz, CD3OD) δ 7.41 (s, 1 H), 7.32 (m, 4 H), 7.29 (m, 1 H), 6.33 (d, 1 H, J = 3.8 Hz), 4.65 (m, 2 H), 4.57 (s, 2 H), 4.37 (t, 1 H, J = 6.3 Hz), 3.89 (m, 1 H), 3.81 (AB dd, 1 H, J = 11.9, 2.9 Hz), 3.67 (AB dd, 1 H, J = 11.9, 5.7 Hz). ¹³ C NMR (100 MHz, CD3OD) δ 164.83 (C), 152.81 (C), 140.71 (CH), 139.48 (C), 129.41 (CH), 128.96 (CH), 128.77 (CH), 111.21 (C), 89.68 (CH), 86.02 (CH), 73.70 (CH2), 72.94 (CH), 71.69 (CH), 66.06 (CH2), 63.93 (CH2). HRMS (ESI ⁺ ) for [MH] ⁺ C17H21N2O7 calculated: 365.13488, observed: 365.13791. Example 22 [0095] 5-[({2-chloro}benzyloxy)methyl]uridine (VAL-2-20F1 – VAL-2-25 – RIID1380 was prepared by the following procedure and with the following results: Treatment of 5-[({2-chloro}benzyloxy)methyl]uracil (772 mg, 2.895 mmol) afforded after two steps 162 mg of product (14%). ¹ H NMR (400 MHz, Methanol-d4) δ 8.15 (s, 1 H), 7.54 (m, 1 H), 7.37 (m, 1 H), 7.27 (m, 2 H), 5.91 (d, 1 H, J = 4.4 Hz), 4.67 (s, 2 H), 4.37 (AB d, 1 H, J = 11.8 Hz), 4.32 (AB d, 1 H, J = 11.8 Hz), 4.18 (m, 2 H), 4.01 (m, 1 H), 3.85 (AB dd, 1 H, J = 12.2, 2.7 Hz), 3.74 (AB dd, 1 H, J = 12.2, 3.1 Hz). ¹³ C NMR (100 MHz, CD3OD) δ 165.18 (C), 152.40 (C), 141.58 (CH), 137.11 (C), 134.07 (C), 130.62 [0001] 4 The compound was first reported in Bertolini, R., Hunziker, J. Aromatic vs. Carbohydrate residues in the major groove: synthesis of 5-[(benzyloxy)methyl]pyrimidine nucleosides and their incorporation into oligonucleotides. Helv. Chim. Acta 2000, 83, 1962-1976. DOI:10.1002/1522-2675(20000809)83:8<1962::AID-HLCA1962> ;3.0.CO;2-8 (CH), 130.27 (CH), 130.07 (CH), 128.05 (CH), 112.18 (C), 90.80 (CH), 86.37 (CH), 75.79 (CH), 71.27 (CH), 71.51 (CH2), 66.23 (CH2), 62.26 (CH2). HRMS (ESI ⁺ ) for [MH] ⁺ C17H20 ³⁵ ClN2O7 calculated: 399.09590, observed: 399.10078. The α-anomer, 1-α-D- ribofuranosyl-5-[({2-chloro}benzyloxy)methyl]uracil (VAL-2-20F2 – VAL-2-26 – RIID1381) obtained: 159 mg (14%). ¹ H NMR (400 MHz, CD3OD) δ 7.52 (m, 1 H), 7.45 (s, 1 H), 7.37 (m, 1 H), 7.27 (m, 2 H), 6.33 (d, 1 H, J = 3.8 Hz), 4.67 (s, 2 H), 4.65 (t, 1 H, J = 3.9 Hz), 4.37 (t, 1 H, J = 6.3 Hz), 4.32 (s, 2 H), 3.90 (m, 1 H), 3.81 (AB dd, 1 H, J = 11.9, 2.9 Hz), 3.67 (AB dd, 1 H, J = 11.9, 5.6 Hz). ¹³ C NMR (100 MHz, CD3OD) δ 164.81 (C), 152.53 (C), 140.73 (CH), 137.05 (C), 134.17 (C), 130.72 (CH), 130.32 (CH), 130.16 (CH), 128.06 (CH), 111.07 (C), 89.68 (CH), 86.01 (CH), 72.94 (CH), 71.68 (CH), 70.62 (CH2), 66.50 (CH2), 63.92 (CH2). HRMS (ESI ⁺ ) for [MH] ⁺ C17H20 ³⁵ ClN2O7 calculated: 399.09590, observed: 399.10108. Example 23 [0096] 5-[(hydroxy)methyl]uridine (RIID1292) was available from Combi-Blocks (catalog #QV-7894). Examples 24 – 38: Synthesis of 5-modified-2′,3′,5′-tris-O-(tert-butyldimethylsilyl) uridines [0097] General procedure for the synthesis of 5-modified-2′,3′,5′-tris-O-(tert- butyldimethylsilyl) uridines. A 5-modified uridine was dissolved in anhydrous dichloromethane under nitrogen atmosphere to achieve concentration ranging from 35 to 140 mM. 4-N,N-dimethylaminopyridine (0.6 eq.) and imidazole (22 eq.) were added. The solution was immersed into ice-water bath and stirred for 10 min followed by addition of tert-butyldimethyl chloride (12 eq.). The reaction mixture was stirred the period from 24 to 36 h while gradually warming up to room temperature. The solvent was evaporated, and the residue was applied onto a chromatography column (SiO2, Hexanes/ EtOAc eluting from 10:1 to 4:1) to afford the product as an oil or a caramel- like solid. Example 24 [0098] 5-[1-phenyl-2,2-(dimethyl)propoxymethyl]-2′,3′,5′-tris -O-(tert- butyldimethylsilyl)uridine (VAL-1-78 was prepared by the following procedure and with the following results: Treatment of 5-[1-phenyl-2,2-(dimethyl)propoxymethyl]uridine (236 mg, 0.561 mmol) afforded 492 mg of product (100%). ¹ H NMR (400 MHz, Chloroform- d) for 1:1 mixture of diastereomers δ 7.48 and 7.47 (2 s, 1 H), 7.25 (m, 5 H), 5.98 and 5.95 (2 d, 1 H, J = 6.4 Hz), 4.15 (m, 1 H), 4.04 (m, 5 H), 3.77 (m, 2 H), 0.91 (s, 9 H), 0.88 (s, 9 H), 0.87 and 0,85 (2 s, 9 H), 0.09 and 0.08 (2 s, 6 H), 0.06 (s, 6 H), 0.02 (s, 3 H), -0.02 and -0.04 (2 s, 3 H). ¹³ C NMR (100 MHz, chloroform-d) for 1:1 mixture of diastereomers δ 162.65 and 162.59 (C), 150.42 and 150.39 (C), 139.28 and 139.21 (C), 137.85 (CH), 128.41 (CH), 127.52 (CH), 127.30 (CH), 112.89 and 112.85 (C), 90.29 and 90.27 (CH), 88.30 and 88.17 (CH), 85.67 and 85.56 (CH), 74.80 and 74.63 (CH), 72.51 and 72.36 (CH), 63.79 and 63.72 (CH2), 63.52 and 63.43 (CH2), 35.63 and 35.60 (C), 26.35 and 26.30 (CH3), 26.07 and 26.06 (CH3), 25.84 and 25.75 (CH3), 25.69 (CH3), 18.49 (C), 18.07 (C), 17.99 and 17.95 (C), -4.44 (CH3), -4.50 (CH3), -4.66 (CH3), -4.77 (CH3), -5.29 and -5.31 (CH3), -5.37 (CH3). Example 25 [0099] 5-[1-(2-methyl)phenyl-2,2-(dimethyl)propoxymethyl]-2′,3′ ,5′-tris-O-(tert- butyldimethylsilyl)uridine (VAL-1-93 was prepared by the following procedure and with the following results: Treatment of 5-[1-(2-methyl)phenyl-2,2- (dimethyl)propoxymethyl]uridine (60 mg, 0.139 mmol) afforded 105 mg of product (97%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 8.77 and 8.74 (br 2 s, 1 H), 7.50 and 7.47 (2 s, 1 H), 7.35 (m, 1 H), 7.14 (m, 3 H), 5.99 and 5.96 (2 d, 1 H, J = 6.4 and 6.3 Hz), 4.46 and 4.41 (2 s, 1 H), 4.16 (m, 1 H), 3.99 (m, 4 H), 3.78 (m, 2 H), 2.36 and 2.34 (2 s, 3 H), 0.93 and 0.91 (2 s, 18 H), 0.87 and 0.86 (2 s, 9 H), 0.10 and 0.09 (2 s, 12 H), 0.04 and 0.03 (2 s, 3 H), -0.01 and -0.03 (2 s, 3 H). ¹³ C NMR (100 MHz, chloroform-d) for 1:1 mixture of diastereomers δ 162.34 and 162.28 (C), 150.25 and 150.18 (C), 137.82 and 137.71 (CH), 137.13 (C), 134.88 (C), 130.18 (CH), 127.86 (CH), 126.98 (CH), 125.30 and 125.27 (CH), 112.94 (C), 88.30 and 88.12 (CH), 85.76 and 85.60 (CH), 84.56 and 84.43 (CH), 74.82 and 74.64 (CH), 72.56 and 72.41 (CH), 63.53 and 63.44 (CH2), 63.39 and 63.35 (CH2), 36.91 and 36.86 (C), 26.08 and 26.04 (CH3), 25.84 (CH3), 25.74 and 23.73 (CH3), 25.67 (CH3), 20.38 (CH3), 18.48 (C), 18.08 (C), 17.99 and 17.95 (C), -4.45 and -4.48 (CH3), -4.65 (CH3), -4.79 (CH3), - 5.28 (CH3), -5.30 and -5.32 (CH3), -5.38 (CH3). Example 26 [0100] 5-[1-(2-chloro)phenyl-2,2-(dimethyl)propoxymethyl]-2′,3′ ,5′-tris-O-(tert- butyldimethylsilyl)uridine (VAL-1-104 was prepared by the following procedure and with the following results: Treatment of 5-[1-(2-chloro)phenyl-2,2- (dimethyl)propoxymethyl]uridine (61 mg, 0.134 mmol) afforded 77 mg of product (72%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 8.95 and 8.93 (br 2 s, 1 H), 7.38 (m, 2 H), 7.23 (m, 1 H), 7.17 (m, 1 H), 7.10 (m, 1 H), 5.89 and 5.86 (2 d, 1 H, J = 6.3 and 6.2 Hz), 4.59 and 4.56 (2 s, 1 H), 4.07 (m, 1 H), 3.96 (m, 3 H), 3.81 (m, 1 H), 3.73 (m, 1 H), 3.67 (m, 1 H), 0.84 and 0.83 (2 s, 18 H), 0.78 (s, 9 H), 0.01 and 0.00 (2 s, 12 H), -0.05 and -0.06 (2 s, 3 H), -0.11 and -0.12 (2 s, 3 H). ¹³ C NMR (100 MHz, chloroform-d) for 1:1 mixture of diastereomers δ 162.40 (C), 150.29 and 150.26 (C), 138.25 and 138.19 (CH), 137.21 (C), 134.88 and 134.78 (C), 129.70 (CH), 129.27 (CH), 128.48 (CH), 126.30 (CH), 112.37 and 112.28 (C), 88.32 (CH), 85.72 and 85.60 (CH), 84.29 and 84.04 (CH), 74.90 and 74.80 (CH), 72.47 and 72.31 (CH), 63.96 and 63.83 (CH2), 63.44 and 63.32 (CH2), 36.91 and 36.83 (C), 26.11 and 26.08 (CH3), 26.03 (CH3), 25.97 (CH3), 25.84 and 25.73 (CH3), 18.51 and 18.47 (C), 18.08 (C), 17.94 (C), - 4.42 (CH3), -4.50 (CH3), -4.67 (CH3), -4.73 and -4.79 (CH3), -5.23 and -5.29 (CH3), -5.30 and -5.36 (CH3). Example 27 [0101] 5-[1-phenyl-1-(cyclohexyl)methoxymethyl]-2′,3′,5′-tris -O-(tert- butyldimethylsilyl)uridine (SSS-1-2 - SSS-1-6 was prepared by the following procedure and with the following results: Treatment of 5-[1-phenyl-1- (cyclohexyl)methoxymethyl]uridine (62 mg, 0.144 mmol) afforded 99 mg of product (87%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 8.06 and 8.05 (br 2 s, 1 H), 7.51 and 7.48 (2 s, 1 H), 7.31 (m, 2 H), 7.25 (m, 3 H), 5.94 (m, 1 H), 4.17 (m, 1 H), 4.04 (m, 5 H), 3.81 (m, 1 H), 3.75 (m, 1 H), 2.02 (m, 1 H), 1.61 (m, 2 H), 1.62 (m, 2 H), 1.24 (m, 6 H), 0.87 (m, 36 H), 0.03 (m, 18 H). ¹³ C NMR (100 MHz, chloroform-d) for 1:1 mixture of diastereomers δ 160.97 (C), 148.99 (C), 139.94 (C), 137.62 and 137.46 (CH), 127.08 and 127.06 (CH), 126.49 (CH), 126.43 (CH), 111.55 and 111.51 (C), 87.46 (CH), 86.70 and 86.36 (CH), 84.72 (CH), 73.79 (CH), 71.38 and 71.31 (CH), 62.48 and 62.35 (CH2), 62.32 and 62.20 (CH2), 43.33 and 43.29 (CH), 30.91 (CH2), 28.64 and 28.57 (CH2), 28.50 and 28.35 (CH2), 28.29 and 28.24 (CH2), 25.50 (CH2), 25.08 and 25.06 (CH3), 25.03 and 25.00 (CH3), 24.71 and 24.70 (CH3), 17.47 (C), 17.05 (C), 16.93 and 16.90 (C), -5.46 (CH3), -5.51 (CH3), -5.69 (CH3), -5.83 (CH3), -6.31 (CH3), -6.34 (CH3). Example 28 [0102] 5-[(1-phenyl)ethoxymethyl]-2′,3′,5′-tris-O-(tert-butyl dimethylsilyl)uridine (VAL-1-145F1 – VAL-1-152F1 was prepared by the following procedure and with the following results: Treatment of 5-[(1-phenyl)ethoxymethyl]uridine (309 mg, 0.817 mmol) afforded 548 mg of product (93%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 8.72 (br s, 1 H), 7.47 and 7.45 (2 s, 1 H), 7.23 (m, 4 H), 7.18 (m, 1 H), 5.85 (d, 1 H, J = 5.9 Hz), 4.42 (m, 1 H), 4.01 (m, 5 H), 3.75 (m, 1 H), 3.65 (m, 1 H), 1.35 and 1.34 (2 d, 3 H, J = 6.4 Hz), 0.83 and 0.82 (2 s, 18 H), 0.77 and 0.76 (2 s, 9 H), 0.01, 0.00 and -0.01 (3 s, 12 H), -0.06 and -0.07 (2 s, 3 H), -0.11 and -0.12 (2 s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 162.35 (C), 150.12 (C), 143.33 (C), 138.84 and 138.48 (CH), 128.48 (CH), 127.59 (CH), 126.25 and 126.18 (CH), 112.38 (C), 88.40 and 88.28 (CH), 85.61 (CH), 78.54 and 78.20 (CH), 75.04 and 74.95 (CH), 72.23 and 72.16 (CH), 63.17 and 63.10 (CH2), 62.84 (CH2), 26.72 (CH3), 26.10 and 25.95 (CH3), 25.83 and 25.72 (CH3), 24.15 and 24.07 (CH3), 18.53 (C), 18.07 (C), 17.94 (C), -4.59 (CH3), -4.51 (CH3), -4.69 (CH3), -4.79 (CH3), -5.35 (CH3). Example 29 [0103] 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)-1-α-D-ribof uranosyl-5-[(1- phenyl)ethoxymethyl]uracil (VAL-1-145F2 – VAL-1-152F2 – VAL-2-5 was prepared by the following procedure and with the following results: Treatment of 1-α-D-ribofuranosyl- 5-[(1-phenyl)propoxymethyl]uracil (62 mg, 0.163 mmol) afforded 105 mg of product (89%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 9.45 (s, 1 H), 7.20 (m, 6 H), 6.16 (d, 1 H, J = 3.7 Hz), 4.83 (br m, 1 H), 4.42 (m, 1 H), 4.28 (m, 1 H), 4.00 (m, 2 H), 3.76 (m, 2 H), 3.58 (m, 1 H), 1.37 (m, 3 H), 0.83 (s, 9 H), 0.81 (s, 9 H), 0.78 and 0.77 (2 s, 9 H), 0.05, 0.02 and 0.00 (3 s, 12 H), -0.06 and -0.10 (2 s, 3 H), - 0.12 and -0.16 (2 s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) δ 162.22 (C), 149.19 (C), 143.22 (C), 135.36 (CH), 128.55 (CH), 127.67 (CH), 126.11 (CH), 112.16 (C), 87.80 (CH), 84.32 (CH), 78.36 and 78.33 (CH), 72.01 and 71.97 (CH), 71.25 (CH), 63.15 (CH2), 63.04 and 62.99 (CH2), 26.00 (CH3), 25.96 (CH3), 25.82 (CH3), 24.74 and 24.01 (CH3), 18.41 (C), 18.11 (C), 17.98 (C), -4.31 (CH3), -4.40 (CH3), -4.64 (CH3), -4.81 and - 4.84 (CH3), -5.29 (2 CH3). Example 30 [0104] 5-[(1-phenyl)propoxymethyl]-2′,3′,5′-tris-O-(tert-buty ldimethylsilyl)uridine (VAL-2-8 – VAL-2-9F2 was prepared by the following procedure and with the following results: Treatment of 5-[(1-phenyl)propoxymethyl]uridine (212 mg, 0.541 mmol) afforded 322 mg of product (81%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 9.64 (br s, 1 H), 7.58 and 7.55 (2 s, 1 H), 7.32 (m, 4 H), 7.28 (m, 1 H), 5.97 and 5.96 (2 d, 1 H, J = 5.8 Hz), 4.27 (t, 1 H, J = 6.6 Hz), 4.11 (m, 2 H), 4.08 (m, 3 H), 3.87 (AB dd, 1 H, J = 11.4, 3.4 Hz), 3.82 (AB dd, 1 H, J = 11.4, 3.2 Hz), 1.85 (m, 1 H), 1.67 (m, 1 H), 0.94 and 0.93 (2 s, 18 H), 0.89 (m, 12 H), 0.12 and 0.11 (2 s, 12 H), 0.06 and 0.05 (3 s, 3 H), 0.03 and 0.01 (2 s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 162.89 and 162.86 (C), 150.45 (C), 142.11 and 142.09 (C), 138.46 and 138.27 (CH), 128.34 and 128.33 (CH), 127.53 (CH), 126.82 and 126.76 (CH), 112.50 (C), 88.69 and 88.52 (CH), 85.43 (CH), 84.22 and 83.95 (CH), 74.92 and 74.88 (CH), 72.19 and 72.15 (CH), 63.30 and 63.23 (CH2), 63.16 and 63.12 (CH2), 31.15 and 31.08 (CH2), 26.10 and 26.08 (CH3), 25.86 (CH3), 25.77 and 25.76 (CH3), 18.52 (C), 18.09 (C), 17.95 (C), 10.32 and 10.29 (CH3), -4.38 (CH3), -4.53 (CH3), -4.71 (CH3), -5.28 (CH3), -5.31 (CH3), -5.35 (CH3). Example 31 [0105] 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)-1-α-D-ribof uranosyl-5-[(1- phenyl)propoxymethyl]uracil (VAL-2-8F2 – VAL-2-10 was prepared by the following procedure and with the following results: Treatment of 1-α-D-ribofuranosyl-5-[(1- phenyl)propoxymethyl]uracil (78 mg, 0.199 mmol) afforded 90 mg of product (62%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 10.12 (br s, 1 H), 7.29 (m, 5 H), 7.24 and 7.23 (2 s, 1 H), 6.25 (d, 1 H, J = 4.5 Hz), 4.94 (m, 1 H), 4.41 (m, 1 H), 4.25 (m, 1 H), 4.12 (m, 2 H), 3.91 (m, 1 H), 3.85 (m, 1 H), 3.69 (m, 1 H), 1.86 (m, 1 H), 1.71 (m, 1 H), 0.94 (s, 9 H), 0.92 (m, 3 H), 0.89 (s, 9 H), 0.87 (s, 9 H), 0.13 (s, 3 H), 0.11 (s, 3 H), 0.05 and 0.04 (2 s, 3 H), 0.03, 0.03, and 0.02 (3 s, 6 H), -0.04 and -0.05 (2 s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) δ 162.21 (C), 149.15 (C), 141.90 (C), 135.69 and 134.94 (CH), 128.41 (CH), 127.64 (CH), 126.67 (CH), 112.20 (C), 88.02 (br CH), 84.31 (CH), 84.01 (CH), 71.97 and 71.90 (CH), 71.30 (CH), 63.30 (CH2), 63.05 and 62.98 (CH2), 31.02 (CH2), 26.00 (CH3), 25.84 (CH3), 24.74 (CH3), 18.42 (C), 18.11 (C), 17.97 (C), 10.26 (CH3), -4.30 (CH3), -4.40 (CH3), -4.64 (CH3), -4.78 (CH3), -4.82 (CH3), - 5.28 (CH3). Example 32 [0106] 5-[(1-phenyl-2-methyl)propoxymethyl]-2′,3′,5′-tris-O-( tert- butyldimethylsilyl)uridine (VAL-2-36 – VAL-2-37F2 was prepared by the following procedure and with the following results: Treatment of 5-[(1-phenyl-2- methyl)propoxymethyl]uridine (226 mg, 0.557 mmol) afforded 208 mg of product (50%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 9.24 and 9.23 (2 s, 1 H), 7.43 and 7.41 (2 s, 1 H), 7.20 (m, 5 H), 5.86 (d, 1 H, J = 5.8 Hz), 4.07 (m, 1 H), 4.00 (m, 5 H), 3.73 (AB dd, 1 H, J = 11.1, 3.8 Hz), 3.66 (AB dd, 1 H, J = 11.1, 2.8 Hz), 1.81 (m, 1 H), 0.89 (m, 3 H), 0.83 (s, 18 H), 0.78 and 0.77 (2 s, 9 H), 0.63 (d, 3 H, J = 6.8 Hz), 0.00 and -0.01 (2 s, 12 H), -0.05 and -0.06 (2 s, 3 H), -0.09 and -0.11 (2 s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 162.69 and 162.66 (C), 150.38 (C), 140.91 (C), 138.19 and 138.16 (CH), 128.10 (CH), 127.47 (2 CH), 112.66 and 112.62 (C), 88.57 and 88.44 (CH), 88.34 and 88.10 (CH), 85.52 (CH), 74.84 and 74.79 (CH), 72.31 and 72.27 (CH), 63.51 and 63.41 (CH2), 63.34 and 63.28 (CH2), 34.84 (CH), 26.08 and 26.07 (CH3), 25.85 (CH3), 25.76 and 25.74 (CH3), 19.09 and 19.04 (CH3), 19.01 and 18.99 (CH3), 18.50 (C), 18.08 (C), 17.94 (C), -4.41 (CH3), - 4.51 (CH3), -4.58 (CH3), -4.69 and -4.75 (CH3), -5.29 and -5.32 (CH3), -5.37 (CH3). Example 33 [0107] 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)-1-α-D-ribof uranosyl-5-[(1-phenyl-2- methyl)propoxymethyl]uracil (VAL-2-38 was prepared by the following procedure and with the following results: Treatment of 1-α-D-ribofuranosyl-5-[(1-phenyl-2- phenyl)propoxymethyl]uracil (51 mg, 0.126 mmol) afforded 53 mg of product (56%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 10.06 (br s, 1 H), 7.37 (m, 6 H), 6.33 (m, 1 H), 5.01 (m, 1 H), 4.50 (m, 1 H), 4.16 (m, 2 H), 4.14 (m, 1 H), 3.98 (m, 1 H), 3.92 (m, 1 H), 3.77 (m, 1 H), 2.03 (m, 1 H), 1.10 (d, 3 H, J = 6.6 Hz), 1.02 (s, 9 H), 0.97 and 0.96 (2 s, 18 H), 0.84 (d, 3 H, J = 6.8 Hz), 0.21 (s, 3 H), 0.11 (s, 3 H), 0.13 and 0.11 (2 s, 3 H), 0.12 and 0.11 (2 s, 6 H), 0.04 and 0.02 (2 s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) δ 162.11 (C), 149.16 (C), 140.73 (C), 135.37 and 134.88 (CH), 128.16 (CH), 127.56 (CH), 127.34 (CH), 112.43 (C), 88.19 (CH), 88.01 (br CH), 84.26 and 84.19 (CH), 71.91 and 71.84 (CH), 71.43 and 71.36 (CH), 63.57 (CH2), 63.02 and 62.95 (CH2), 34.83 (CH), 25.99 (CH3), 25.96 (CH3), 25.83 (CH3), 19.04 (CH3), 19.00 (CH3), 18.43 and 18.40 (C), 18.10 (C), 17.98 (C), -4.29 (CH3), -4.41 (CH3), -4.64 (CH3), -4.79 (CH3), -4.83 (CH3), -5.28 (CH3). Example 34 [0108] 5-[(benzyloxy)methyl]-2′,3′,5′-tris-O-(tert-butyldimet hylsilyl)uridine (VAL-1- 113F1 – VAL-1-119F1 was prepared by the following procedure and with the following results: Treatment of 5-[1-(benzyloxy)methyl]uridine (98 mg, 0.269 mmol) afforded 114 mg of product (60%). ¹ H NMR (400 MHz, Chloroform-d) δ 8.10 (s, 1 H), 7.65 (s, 1 H), 7.34 (m, 5 H), 6.00 (d, 1 H, J = 6.4 Hz), 4.58 (s, 2 H), 4.28 (s, 2 H), 4.16 (dd, 1 H, J = 6.4, 4.6 Hz), 4.07 (m, 1 H), 4.04 (m, 1 H), 3.85 (dd, 1 H, J = 11.5, 2.9 Hz), 3.74 (dd, 1 H, J = 11.5, 2.6 Hz), 0.93 (s, 9 H), 0.92 (s, 9 H), 0.86 (s, 9 H), 0.10 (s, 6 H), 0.09 (s, 3 H), 0.08 (s, 3 H), 0.03 (s, 3 H), -0.03 (s, 3 H). ¹³ C NMR (100 MHz, Chlorofrorm-d) δ 162.57 (C), 150.22 (C), 138.82 (CH), 137.94 (C), 128.29 (CH), 127.75 (CH), 127.69 (CH), 112.05 (C), 87.95 (CH), 85.80 (CH), 75.10 (CH), 72.83 (CH2), 72.26 (CH), 64.30 (CH2), 63.12 (CH2), 26.11 (CH3), 25.84 (CH3), 25.73 (CH3), 18.55 (C), 18.08 (C), 17.93 (C), - 4.42 (CH3), -4.49 (CH3), -4.68 (CH3), -4.76 (CH3), -5.39 (2 CH3). Example 35 [0109] 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)-1-α-D-ribof uranosyl-5- [(benzyloxy)methyl]uracil (VAL-1-113F2 – VAL-1-119F2 was prepared by the following procedure and with the following results: Treatment of 1-α-D-ribofuranosyl-5- [(benzyloxy)methyl]uracil (18 mg, 0.048 mmol) afforded 10 mg of product (29%). ¹ H NMR (400 MHz, Chloroform-d) δ10.03 (s, 1 H), 7.25 (m, 5 H), 7.17 (s, 1 H), 6.24 (d, 1 H, J = 4.2 Hz), 4.92 (m, 1 H), 4.55 (s, 2 H), 4.36 (m, 1 H), 4.21 (s, 2 H), 3.88 (m, 1 H), 3.82 (m, 1 H), 3.67 (m, 1 H), 0.98 (s, 9 H), 0.89 (s, 9 H), 0.82 (s, 9 H), 0.11 (s, 3 H), 0.08 (s, 3 H), 0.06 (s, 3 H), 0.00 (s, 3 H), -0.01 (s, 3 H), -0.08 (s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) δ 162.33 (C), 152.37 (C), 137.81 (CH), 136.14 (C), 128.46 (CH), 127.82 (CH), 127.74 (CH), 111.71 (C), 87.83 (CH), 84.43 (CH), 73.01 (CH), 72.03 (CH2), 71.24 (CH), 64.75 (CH2), 63.05 (CH2), 25.99 (CH3), 25.97 (CH3), 25.82 (CH3), 18.43 (C), 18.11 (C), 17.98 (C), -4.31 (CH3), -4.38 (CH3), -4.64 (CH3), -4.81 (CH3), -5.28 (2 CH3). Example 36 [0110] 5-[({2-chloro}benzyloxy)methyl]-2′,3′,5′-tris-O-(tert- butyldimethylsilyl)uridine (VAL-2-22F2 was prepared by the following procedure and with the following results: Treatment of 5-[({2-chloro}benzyloxy)methyl]uridine (160 mg, 0.401 mmol) afforded 48 mg of product (41%). ¹ H NMR (400 MHz, Chloroform-d) δ 8.91 (br s, 1 H), 7.68 (s, 1 H), 7.49 (m, 1 H), 7.32 (m, 1 H), 7.21 (m, 2 H), 6.00 (d, 1 H, J = 6.2 Hz), 4.67 (s, 2 H), 4.36 (AB d, 1 H, J = 12.0 Hz), 4.33 (AB d, 1 H, J = 12.0 Hz), 4.16 (dd, 1 H, J = 6.2, 4.6 Hz), 4.05 (m, 2 H), 3.86 (AB dd, 1 H, J = 11.4, 2.9 Hz), 3.73 (AB dd, 1 H, J = 11.4, 2.7 Hz), 0.92 and 0.91 (2 s, 18 H), 0.86 (s, 9 H), 0.09 (s, 9 H), 0.07 (s, 3 H), 0.03 (s, 3 H), -0.02 (s, 3 H). ¹³ C NMR (100 MHz, Chlorofrorm-d) δ 162.58 (C), 150.22 (C), 139.13 (CH), 135.69 (C), 132.82 (C), 129.22 (CH), 129.07 (CH), 128.08 (CH), 126.79 (CH), 111.78 (C), 88.00 (CH), 85.81 (CH), 75.16 (CH), 72.27 (CH), 69.66 (CH2), 64.76 (CH2), 63.14 (CH2), 26.09 (CH3), 25.83 (CH3), 25.73 (CH3), 18.54 (C), 18.08 (C), 17.93 (C), -4.41 (CH3), -4.50 (CH3), -4.69 (CH3), -4.76 (CH3), -5.38 (CH3), -5.41 (CH3). Example 37 [0111] 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)-1-α-D-ribof uranosyl-5-[({2- chloro}benzyloxy)methyl]uracil (VAL-2-24 was prepared by the following procedure and with the following results: Treatment of 1-α-D-ribofuranosyl-5-[({2- chloro}benzyloxy)methyl]uracil (138 mg, 0.348 mmol) afforded 122 mg of product (47%). ¹ H NMR (400 MHz, Chloroform-d) δ 9.29 (br s, 1 H), 7.42 (m, 1 H), 7.30 (m, 1 H), 7.21 (m, 2 H), 7.15 (m, 1 H), 6.23 (d, 1 H, J = 4.8 Hz), 4.93 (t, 1 H, J = 5.0 Hz), 4.64 (s, 2 H), 4.35 (t, 1 H, J = 4.7 Hz), 4.32 (AB d, 1 H, J = 13.6 Hz), 4.29 (AB d, 1 H, J = 13.8 Hz), 3.89 (m, 1 H), 3.82 (AB dd, 1 H, J = 10.9, 6.1 Hz), 3.73 (AB dd, 1 H, J = 10.9, 5.1 Hz), 0.88 (s, 9 H), 0.84 (s, 9 H), 0.82 (s, 9 H), 0.07 (s, 3 H), 0.05 (s, 3 H), 0.00 (s, 3 H), -0.01 (s, 3 H), -0.02 (s, 3 H), -0.10 (s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) δ 162.37 (C), 152.70 (C), 136.47 (CH), 135.56 (C), 132.98 (C), 129.56 (CH), 129.34 (CH), 128.88 (CH), 126.84 (CH), 111.40 (C), 87.85 (CH), 84.47 (CH), 72.06 (CH), 71.21 (CH), 69.96 (CH2), 63.07 (CH2), 62.73 (CH2), 25.98 (CH3), 25.97 (CH3), 25.82 (CH3), 18.42 (C), 18.10 (C), 17.97 (C), -4.32 (CH3), -4.39 (CH3), -4.65 (CH3), -4.81 (CH3), -5.29 (2 CH3). Example 38 [0112] 5-[(tert-butyldimethylsilyloxy)methyl]-2′,3′,5′-tris-O -(tert- butyldimethylsilyl)uridine (VAL-1-136 was prepared by the following procedure and with the following results: Treatment of 5-[(tert-butyldimethylsilyloxy)methyl]uridine (233 mg, 0.850 mmol) afforded 400 mg of product (64%). ¹ H NMR (400 MHz, Chloroform-d) δ 9.55 (s, 1 H), 7.46 (s, 1 H), 5.94 (d, 1 H, J = 6.1 Hz), 4.47 (AB d, 1 H, J = 13.3 Hz), 4.41 (AB d, 1 H, J = 13.3 Hz), 4.18 (t, 1 H, J = 5.2 Hz), 4.06 (m, 1 H), 4.01 (m, 1 H), 3.75 (d, 2 H, J = 4.2 Hz), 0.93 (s, 9 H), 0.91 (s, 9 H), 0.90 (s, 9 H), 0.85 (s, 9 H), 0.10 (s, 12 H), 0.09 (s, 6 H), 0.02 (s, 3 H), -0.03 (s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) δ 162.68 (C), 150.45 (C), 137.44 (CH), 114.56 (C), 88.77 (CH), 85.40 (CH), 74.43 (CH), 72.34 (CH2), 72.26 (CH), 63.42 (CH2), 57.91 (CH2), 26.05 (CH3), 25.91 (CH3), 25.84 (CH3), 25.74 (CH3), 18.48 (C), 18.32 (C), 18.05 (C), 17.93 (C), -4.45 (CH3), -4.55 (CH3), -4.67 (CH3), -4.79 (CH3), -5.28 (CH3), -5.35 (CH3), -5.37 (CH3), -5.38 (CH3). Examples 39 – 52: sulfonylation of 5-modified-2′,3′,5′-tris-(tert-butyldimethylsilyl) uridines [0113] General procedure for the sulfonylation of 5-modified-2′,3′,5′-tris-(tert- butyldimethylsilyl) uridines. A 5-modified- 2′,3′,5′-tris-(tert-butyldimethylsilyl)uridine was dissolved in anhydrous dichloromethane under nitrogen atmosphere to achieve concentration ranging from 45 to 120 mM. 4-N,N-dimethylaminopyridine (0.2 eq) and imidazole (10 eq) were added. The solution was immersed into ice-water bath and stirred for 15 min followed by addition of 2,4,6-triisopropylbenzenesulfonyl chloride (2 eq). The reaction mixture was stirred the period from 10 to 25 h while gradually warming up to room temperature. The solvent was evaporated, and the residue was applied onto a chromatography column (SiO2, Hexanes/ EtOAc eluting from 15:1 to 4:1) to afford the product as a white fluffy solid, and, occasionally, the starting material as a waxy solid. Example 39 [0114] 5-[1-phenyl-2,2-(dimethyl)propoxymethyl]-4-O-(2,4,6- triisopropylbenzenesulfonyl)-2′,3′,5′-tris-O-(tert-but yldimethylsilyl)uridine (VAL-1-79 - VAL-1-82 was prepared by the following procedure and with the following results: Treatment of 5-[1-phenyl-2,2-(dimethyl)propoxymethyl]-2′,3′,5′-tris -O-(tert- butyldimethylsilyl)uridine (267 mg, 0.350 mmol) afforded 225 mg of product (62%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 7.87 and 7.85 (2 s, 1 H), 7.24 (m, 5 H), 7.10 (s, 2 H), 5.83 and 5.82 (2 d, 1 H, J = 4.3 and 4.2 Hz), 4.09 (m, 3 H), 4.01 (m, 2 H), 3.93 (m, 1 H), 3.86 (m, 3 H), 3.68 (AB dd, 1 H, J = 11.5, 2.8 Hz), 2.82 (sep, 1 H, J = 6.9 Hz), 1.17 (m, 18 H), 0.83 and 8.82 (2 s, 27 H), 0.74 (s, 9 H), 0.00 (m, 12 H), -0.10 and -0.11 (2 s, 3 H), -0.17 and -0.18 (2 s, 3 H). ¹³ C NMR (100 MHz, chloroform-d) for 1:1 mixture of diastereomers δ 165.81 and 165.72 (C), 154.21 (C), 153.45 (C), 151.19 and 151.17 (C), 144.71 and 144.68 (CH), 138.74 (C), 131.23 and 131.16 (C),128.44 (CH), 127.75 (CH), 127.49 and 127.47 (CH), 123.96 (CH), 105.96 and 105.77 (C), 90.67 and 90.29 (CH), 90.15 and 89.99 (CH), 85.15 and 85.10 (CH), 76.10 (CH), 71.64 and 71.57 (CH), 63.41 and 63.23 (CH2), 63.01 and 62.89 (CH2), 35.66 and 35.62 (C), 34.24 (CH), 29.62 (CH), 26.32 and 26.31 (CH3), 26.14 (CH3), 25.84 (CH3), 25.77 (CH3), 24.55 and 24.43 (CH3), 23.50 (CH3), 18.57 (C), 18.05 (C), 17.95 (C), -4.26 (CH3), -4.73 and -4.75 (CH3), -4.85 (CH3), -4.88 (CH3), -5.11 and -5.14 (CH3), -5.26 and -5.34 (CH3). Starting material retrieved: 42 mg (16%). Example 40 [0115] 5-[1-(2-methyl)phenyl-2,2-(dimethyl)propoxymethyl]-4-O-(2,4, 6- triisopropylbenzenesulfonyl)-2′,3′,5′-tris-O-(tert-but yldimethylsilyl)uridine (VAL-1-94 was prepared by the following procedure and with the following results: Treatment of 5-[1-(2- methyl)phenyl-2,2-(dimethyl)propoxymethyl]-2′,3′,5′-tr is-O-(tert-butyldimethylsilyl)uridine (105 mg, 0.139 mmol) afforded 89 mg of product (63%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 7.95 and 7.89 (2 s, 1 H), 7.48 (br m, 1 H), 7.18 (m, 5 H), 5.92 and 5.91 (2 d, 1 H, J = 4.6 Hz), 4.26 (m, 2 H), 4.08 (m, 4 H), 3.90 (m, 3 H), 3.76 (m, 1 H), 2.89 (sep, 1 H, J = 6.9 Hz), 2.37 and 2.35 (2 s, 3 H), 1.25 (m, 18 H), 0.95 (s, 9 H), 0.91 and 0.89 (2 s, 18 H), 0.80 (s, 9 H), 0.09 and 0.08 (2 s, 3 H), 0.07 and 0.06 (2 s, 9 H), -0.04 and -0.05 (2 s, 3 H), -0.12 and -0.14 (2 s, 3 H). ¹³ C NMR (100 MHz, chloroform-d) for 1:1 mixture of diastereomers δ 165.80 (C), 154.19 (C), 153.50 (C), 151.21 and 151.18 (C), 144.60 (CH), 136.98 and 136.88 (C), 131.21 and 131.17 (C), 130.25 (CH), 128.01 (CH), 127.13 and 127.10 (CH), 125.67 (CH), 123.95 (CH), 106.06 and 105.76 (C), 89.92 (CH), 85.30 and 85.09 (CH), 84.91 and 84.22 (CH), 76.28 and 76.20 (CH), 71.73 and 71.52 (CH), 63.19 and 62.80 (CH2), 62.98 (CH2), 36.91 and 36.87 (C), 34.23 (CH), 29.73 and 29.71 (CH), 26.36 (CH3), 26.15 and 26.13 (CH3), 25.83 (CH3), 25.75 (CH3), 24.51 and 24.50 (CH3), 24.46 and 24.39 (CH3), 23.59 (CH3), 20.32 (CH3), 18.58 and 18.53 (C), 18.06 and 18.04 (C), 17.93 (C), -4.27 (CH3), -4.76 and -4.81 (CH3), -4.84 and -4.86 (CH3), -4.88 (CH3), -5.06 and -5.17 (CH3), -5.31 and - 5.39 (CH3). Starting material retrieved: 24 mg (23%). Example 41 [0116] 5-[1-(2-chloro)phenyl-2,2-(dimethyl)propoxymethyl]-4-O-(2,4, 6- triisopropylbenzenesulfonyl)-2′,3′,5′-tris-O-(tert-but yldimethylsilyl)uridine (VAL-1-105 was prepared by the following procedure and with the following results: Treatment of 5- [1-(2-chloro)phenyl-2,2-(dimethyl)propoxymethyl]-2′,3′,5 ′-tris-O-(tert- butyldimethylsilyl)uridine (77 mg, 0.097 mmol) afforded 43 mg of product (42%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 7.89 (s, 1 H), 7.53 (m, 1 H), 7.29 (m, 1 H), 7.19 (m, 2 H), 7.11 and 7.08 (2 s, 2 H), 5.84 and 5.82 (2 d, 1 H, J = 4.5 and 4.3 Hz), 4.62 and 4.61 (2 s, 1 H), 4.19 (m, 2 H), 3.91 (m, 6 H), 3.68 (m, 1 H), 2.83 (m, 2 H), 1.19 (m, 18 H), 0.90 and 0.89 (2 s, 9 H), 0.85, 0.83, 0.82, and 0.81 (4 s, 18 H), 0.75 and 0.73 (2 s, 9 H), 0.04 and 0.03 (2 s, 3 H), 0.01, 0.00, -0.01, and -0.02 (4 s, 9 H), -0.08 and -0.13 (2 s, 3 H), -0.14 and -0.22 (2 s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 165.96 and 165.89 (C), 154.22 and 154.20 (C), 153.48 and 150.40 (C), 151.24 and 151.18 (C), 144.95 and 144.79 (CH), 136.72 (C), 134.84 and 134.73 (C), 131.19 and 131.16 (C), 129.91 and 129.80 (CH), 129.27 (CH), 128.61 and 128.57 (CH), 126.76 and 126.72 (CH), 123.96 (CH), 105.55 and 105.23 (C), 88.94 and 88.88 (CH), 85.25 and 84.91 (CH), 84.77 and 82.21 (CH), 76.38 and 76.26 (CH), 71.55 and 71.29 (CH), 63.73 and 63.41 (CH2), 62.79 and 62.62 (CH2), 36.84 and 36.78 (C), 34.25 and 34.22 (CH), 29.61 (CH), 26.18 (CH3), 26.16 and 26.07 (CH3), 25.93 and 25.89 (CH3), 25.83 and 25.76 (CH3), 24.50 and 24.39 (CH3), 23.60 (CH3), 18.64 and 18.56 (C), 18.07 and 18.04 (C), 17.95 and 17.93 (C), -4.24 (CH3), -4.68 and -4.79 (CH3), -4.86 and -4.87 (CH3), -4.92 and -4.94 (CH3), -5.11 (CH3), -5.28 and -5.37 (CH3). Example 42 [0117] 5-[1-phenyl-1-(cyclohexyl)methoxymethyl]-4-O-(2,4,6- triisopropylbenzenesulfonyl)-2′,3′,5′-tris-O-(tert-but yldimethylsilyl)uridine (VAL-1-85 was prepared by the following procedure and with the following results: Treatment of 5-[1- phenyl-1-(cyclohexyl)methoxymethyl]- 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)uridine (109 mg, 0.138 mmol) afforded 97 mg of product (67%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 7.86 and 7.84 (2 s, 1 H), 7.27 (m, 5 H), 7.13 and 7.11 (2 s, 2 H), 5.95 (m, 1 H), 4.50 (m, 1H), 4.21 (m, 1 H), 4.01 (m, 5 H), 3.85 (m, 1 H), 3.78 (m, 1 H), 2.81 (m, 2 H), 2.00 (m, 1 H), 1.64 (m, 2 H), 1.61 (m, 2 H), 1.24 (m, 24 H), 0.87 (m, 36 H), -0.01 (m, 18 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 161.04 (C), 155.60 (C), 154.99 and 154.12 (C), 151.19 and 150.40 (C), 140.68 and 140.45 (CH), 132.15 and 131.29 (C), 130.25 (C), 128.28 (CH), 127.69 and 127.63 (CH), 127.59 and 127.36 (CH), 124.30 and 124.23 (CH), 105.86 (C), 90.37 and 90.32 (CH), 88.03 and 87.72 (CH), 85.00 (CH), 83.88 (CH), 72.09 and 72.38 (CH), 63.44 and 63.14 (CH2), 62.97 and 62.58 (CH2), 44.46 and 44.39 (CH), 34.41 and 34.31 (CH), 30.91 (CH2), 29.74 and 29.72 (CH2), 29.63 and 29.49 (CH2), 29.46 and 29.35 (CH2), 25.97 and 25.94 (CH2), 25.92 and 25.86 (CH3), 25.79 and 25.76 (CH3), 24.82 and 24.57 (CH3), 24.47 and 24.40 (CH3), 23.52 and 23.47 (CH3), 18.60 and 18.41 (C), 18.06 and 18.01 (C), 17.96 and 17.88 (C), -4.22 and -4.28 (CH3), -4.49 (CH3), -4.71 and -4.77 (CH3), -4.86 and -4.96 (CH3), -5.07 and -5.12 (CH3), -5.27 and -5.33 (CH3). Example 43 [0118] 5-[1-(phenyl)ethoxymethyl]-4-O-(2,4,6-triisopropylbenzenesul fonyl)-2′,3′,5′- tris-O-(tert-butyldimethylsilyl)uridine (VAL-1-153 was prepared by the following procedure and with the following results: Treatment of 5-[1-(phenyl)ethoxymethyl]- 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)uridine (107 mg, 0.149 mmol) afforded 30 mg of product (20%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 8.05 and 8.04 (2 s, 1 H), 7.37 (m, 4 H), 7.32 (m, 1 H), 7.18 (s, 2 H), 5.85 and 5.83 (2 d, 1 H, J = 3.9 Hz), 4.51 (m, 1 H), 4.25 (m, 2 H), 4.09 (m, 5 H), 3.96 (m, 2 H), 3.76 (m, 1 H), 2.90 (m, 2 H), 1.48 (d, 1 H, J = 6.4 Hz), 1.24 (m, 18 H), 0.92 and 0.90 (2 s, 18 H), 0.83 and 0.82 (2 s, 9 H), 0.08 (m, 12 H), 0.00 and -0.01 (2 s, 3 H), -0.04 and -0.06 (2 s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 165.90 and 165.84 (C), 154.21 and 153.54 (C), 151.21 (C), 145.11 and 144.93 (CH), 142.87 (C), 139.24 (C), 131.18 and 131.15 (C), 128.68 and 128.53 (CH), 127.74 (CH), 126.28 (CH), 123.97 (CH), 105.45 (C), 90.29 (CH), 84.77 (CH), 78.91 and 78.61 (CH), 76.24 and 76.16 (CH), 71.05 and 70.94 (CH), 62.92 and 62.72 (CH2), 62.47 and 62.34 (CH2), 34.24 (CH), 29.61 (CH), 26.21 and 26.17 (CH3), 25.84 and 25.78 (CH3), 24.62 and 24.60 (CH3), 24.40 (CH3), 24.14 and 24.06 (CH3), 23.49 (CH3), 18.64 (C), 18.04 (C), 17.96 (C), -4.16 and -4.17 (CH3), -4.63 and -4.67 (CH3), -4.89 and -4.87 (CH3), -4.91 (CH3), -5.04 and -5.18 (CH3), -5.38 (CH3). Example 44 [0119] 3-N-(2,4,6-triisopropylbenzenesulfonyl)-2′,3′,5′-tris- O-(tert- butyldimethylsilyl)-1-α-D-ribofuranosyl-5-[1-(phenyl)ethoxy methyl]uracil (VAL-1-147F1 was prepared by the following procedure and with the following results: Treatment of 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)-1-α-D-ribof uranosyl-5-[1- (phenyl)ethoxymethyl]uracil (46 mg, 0.064 mmol) afforded 28 mg of product (44%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 8.14 (s, 1 H), 7.35 (m, 5 H), 7.19 (s, 2 H), 6.09 (d, 1 H, J = 3.6 Hz), 4.55 (m, 2 H), 4.27 (m, 1 H), 4.18 (m, 2 H), 4.00 (m, 2 H), 3.77 (m, 1 H), 3.70 (m, 1 H), 3.51 (m, 1 H), 2.91 (m, 1 H), 1.51 (d, 1 H, J = 6.4 Hz), 1.25 (m, 12 H), 1.21 (m, 6 H), 0.87 (2 s, 9 H), 0.84 and 0.83 (2 s, 9 H), 0.78 (s, 9 H), 0.04 (s, 3 H), 0.00 (s, 3 H), -0.02 and -0.03 (2 s, 3 H), -0.04 and -0.05 (2 s, 3 H), -0.08 (s, 3 H), -0.23 (s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 161.12 (C), 154.96 (C), 151.96 (C), 143.12 (C), 132.24 (CH), 130.24 (C), 128.62 (CH), 127.77 (CH), 126.11 (CH), 124.21 (CH), 112.67 (C), 88.54 (CH), 83.95 and 83.91 (CH), 78.36 (CH), 71.97 (CH), 71.40 (CH), 63.03 (CH2), 62.95 (CH2), 34.29 (CH), 31.94 (CH), 29.71 and 29.75 (CH), 26.18 and 26.14 (CH3), 25.98 and 25.94 (CH3), 24.70 (CH3), 24.35 (CH3), 23.56 (CH3), 23.45 (CH3), 23.45 (CH3), 18.37 (C), 18.00 (C), 17.87 (C), -4.31 (CH3), -4.49 (CH3), -4.78 (CH3), -4.97 (CH3), -5.33 (CH3), - 5.34 (CH3). Example 45 [0120] 5-[1-(phenyl)propoxymethyl]-4-O-(2,4,6-triisopropylbenzenesu lfonyl)- 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)uridine (VAL-2-13F1 was prepared by the following procedure and with the following results: Treatment of 5-[1-(phenyl)propoxymethyl]- 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)uridine (314 mg, 0.427 mmol) afforded 138 mg of product (32%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 8.01 and 8.00 (2 s, 1 H), 7.33 (m, 5 H), 7.18 (s, 2 H), 5.86 (m, 1 H), 4.18 (m, 3 H), 4.09 (m, 2 H), 3.96 (m, 3 H), 3.75 (m, 2 H), 2.90 (m, 1 H), 1.86 (m, 1 H), 1.70 (m, 1 H), 1.24 (m, 18 H), 0.90 (m, 21 H), 0.81 (s, 9 H), 0.08, 0.07, and 0.06 (3 s, 12 H), -0.01 and -0.02 (2 s, 3 H), -0.08 (s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 165.88 (C), 154.21 (C), 153.54 (C), 151.22 (C), 144.98 and 144.87 (CH), 141.60 and 141.55 (C), 131.17 (C), 128.56 and 128.55 (CH), 127.74 (CH), 126.86 (CH), 123.96 (CH), 105.65 and 105.57 (C), 90.31 and 90.05 (CH), 84.96 and 84.89 (CH), 84.68 and 84.28 (CH), 76.27 and 76.13 (CH), 71.20 (CH), 63.01 and 62.80 (CH2), 62.63 and 62.53 (CH2), 34.24 (CH), 31.13 and 31.03 (CH2), 29.62 (CH), 26.19 and 26.16 (CH3), 25.84 and 25.77 (CH3), 24.62 (CH3), 24.57 (CH3), 24.44 and 24.39 (CH3), 23.50 (CH3), 18.61 (C), 18.04 (C), 17.96 (C), 10.29 and 10.23 (CH3), -4.20 (CH3), -4.69 (CH3), -4.88 (CH3), -5.07 (CH3), -5.18 (CH3), -5.34 and -5.38 (CH3). Example 46 [0121] 3-N-(2,4,6-triisopropylbenzenesulfonyl)-2′,3′,5′-tris- O-(tert- butyldimethylsilyl)-1-α-D-ribofuranosyl-5-[1-(phenyl)propox ymethyl]uracil (VAL-2-9F1 was prepared by the following procedure and with the following results: Treatment of 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)-1-α-D-ribof uranosyl-5-[1- (phenyl)propoxymethyl]uracil (173 mg, 0.234 mmol) afforded 162 mg of product (69%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 8.19 and 8.18 (2 s, 1 H), 7.33 (m, 5 H), 7.21 (s, 2 H), 6.11 (d, 1 H, J = 2.3 Hz), 4.58 (m, 1 H), 4.30 (m, 2 H), 4.18 (m, 2 H), 4.03 (m, 2 H), 3.79 (m, 1 H), 3.74 (m, 1 H), 3.53 (m, 1 H), 2.93 (m, 1 H), 1.91 (m, 1 H), 1.77 (m, 1 H), 1.25 (m, 18 H), 0.97 (t, 3 H, J = 7.4 Hz), 0.89 (s, 9 H), 0.86 and 0.85 (2 s, 9 H), 0.80 and 0.79 (2 s, 9 H), 0.06 (s, 3 H), 0.03 (s, 3 H), -0.00 and -0.01 (2 s, 3 H), -0.02 and -0.03 (2 s, 3 H), -0.07 (s, 3 H), -0.22 (s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 161.07 (C), 154.96 (C), 151.98 (C), 141.88 (C), 132.15 (CH), 130.26 (C), 128.50 (CH), 127.77 (CH), 126.63 (CH), 124.22 (CH), 112.74 (C), 88.61 (br CH), 84.20 and 84.17 (CH), 83.91 and 83.86 (CH), 72.04 (CH), 71.41 and 71.36 (CH), 63.22 (CH2), 63.02 and 62.95 (CH2), 34.30 (CH), 31.15 (CH2), 29.32 (CH), 25.97 and 25.94 (CH3), 25.90 (CH3), 25.74 (CH3), 24.54 and 24.52 (CH3), 23.50 and 23.46 (CH3), 18.40 and 18.38 (C), 18.01 (C), 17.87 (C), 10.33 (CH3), - 4.29 (CH3), -4.49 (CH3), -4.78 (CH3), -4.97 (CH3), -5.32 (CH3), -5.34 (CH3). Example 47 [0122] 5-[1-(phenyl-2-methyl)propoxymethyl]-4-O-(2,4,6- triisopropylbenzenesulfonyl)-2′,3′,5′-tris-O-(tert-but yldimethylsilyl)uridine (VAL-2-41 was prepared by the following procedure and with the following results: Treatment of 5-[1- (phenyl-2-methyl)propoxymethyl]-2′,3′,5′-tris-O-(tert- butyldimethylsilyl)uridine (208 mg, 0.278 mmol) afforded 106 mg of product (38%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 7.97 and 7.95 (2 s, 1 H), 7.31 (m, 5 H), 7.22 (s, 2 H), 5.89 and 5.87 (2 d, 1 H, J = 4.4 and 4.2 Hz), 4.23 (m, 2 H), 4.14 (m, 1 H), 4.08 (m, 3 H), 3.92 (m, 3 H), 3.75 (m, 1 H), 2.91 (m, 1 H), 1.94 (m, 1 H), 1.27 (m, 18 H), 1.02 and 1.01 (2 d, 3 H, J = 6.8 Hz), 0.90 and 0.89 (2 s, 18 H), 0.81 and 0.80 (2 s, 9 H), 0.73 (d, 3 H, J = 6.7 and 6.5 Hz), 0.07, and 0.05 (2 s, 12 H), -0.03 (s, 3 H), -0.09 and -0.10 (2 s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 165.88 and 165.77 (C), 155.60 (C), 154.20 (C), 153.53 and 153.49 (C), 144.85 and 144.81 (CH), 140.40 and 140.36 (C), 131.21 and 131.17 (C), 128.33 and 128.30 (CH), 127.67 and 127.54 (CH), 124.30 (CH), 123.96 and 123.78 (CH), 105.81 and 105.66 (C), 90.32 and 89.94 (CH), 88.74 and 84.24 (CH), 85.08 and 84.88 (CH), 76.23 and 76.09 (CH), 71.42 (CH), 63.17 and 62.97 (CH2), 62.81 and 62.69 (CH2), 34.85 and 34.82 (CH), 34.40 and 34.24 (CH), 29.73 and 29.63 (CH), 26.16 and 26.15 (CH3), 25.84 and 25.76 (CH3), 24.62 (CH3), 24.55 (CH3), 24.45 and 24.39 (CH3), 23.50 and 23.46 (CH3), 19.17 and 19.12 (CH3), 18.96 and 18.89 (CH3), 18.59 (C), 18.05 (C), 17.94 (C), -4.22 and -4.24 (CH3), -4.72 (CH3), -4.86 (CH3), -4.90 (CH3), -5.11 and -5.16 (CH3), -5.30 and -5.36 (CH3). Example 48 [0123] 3-N-(2,4,6-triisopropylbenzenesulfonyl)-2′,3′,5′-tris- O-(tert- butyldimethylsilyl)-1-α-D-ribofuranosyl-5-[1-(phenyl-2-meth yl)propoxymethyl]uracil (VAL- 2-37F1 was prepared by the following procedure and with the following results: Treatment of 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)-1-α-D-ribof uranosyl-5-[1-(phenyl-2- methyl)propoxymethyl]uracil (173 mg, 0.234 mmol) afforded 162 mg of product (69%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 8.14 (2 s, 1 H), 7.31 (m, 2 H), 7.24 (m, 3 H), 7.16 (s, 2 H), 6.04 (m, 1 H), 4.51 (AB dd, 1 H, J = 9.2, 5.0 Hz), 4.10 (m, 4 H), 3.98 (m, 3 H), 3.74 (AB dd, 1 H, J = 10.4, 5.0 Hz), 3.67 (m, 1 H), 3.48 (m, 1 H), 2.87 (m, 1 H), 2.00 (m, 1 H), 1.21 (m, 18 H), 1.02 (d, 3 H, J = 6.6 Hz), 0.88 (m, 3 H), 0.83 (s, 9 H), 0.80 and 0.78 (2 s, 9 H), 0.74 and 0.73 (2 s, 9 H), 0.00 (s, 3 H), -0.02 and -0.03 (2 s, 3 H), -0.06 and -0.10 (2 s, 3 H), -0.07 and -0.08 (2 s, 3 H), - 0.12 and -0.13 (2 s, 3 H), -0.28 (s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 161.03 (C), 154.95 (C), 152.00 (C), 140.66 (C), 132.48 (CH), 130.25 (C), 128.28 (CH), 127.71 (CH), 127.31 (CH), 124.21 (CH), 112.77 (C), 88.61 (br CH), 88.44 and 88.39 (CH), 83.89 and 83.84 (CH), 72.06 (CH), 71.41 and 71.40 (CH), 63.46 (CH2), 63.03 and 62.96 (CH2), 38.75 (CH), 34.95 and 34.30 (CH), 29.33 (CH), 25.96 and 25.93 (CH3), 25.90 (CH3), 25.74 (CH3), 24.59 and 24.55 (CH3), 23.71 and 23.46 (CH3), 19.11 (CH3), 18.93 (CH3),18.40 and 18.37 (C), 18.01 (C), 17.87 (C), -4.29 (CH3), -4.50 (CH3), -4.79 (CH3), -4.97 (CH3), -5.34 (2 CH3). Example 49 [0124] 5-[(benzyloxy)methyl]-4-O-(2,4,6-triisopropylbenzenesulfonyl )-2′,3′,5′-tris- O-(tert-butyldimethylsilyl)uridine (VAL-1-121F1a – VAL-1-126 was prepared by the following procedure and with the following results: Treatment of 5-[(benzyloxy)methyl]- 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)uridine (16 mg, 0.023 mmol) afforded 10 mg of product (56%). ¹ H NMR (400 MHz, Chloroform-d) δ 8.11 (s, 1 H), 7.32 (m, 5 H), 7.18 (s, 2 H), 5.87 (d, 1 H, J = 4.1 Hz), 4.58 (s, 2 H), 4.27 (m, 4 H), 4.08 (m, 2 H), 3.95 (m, 2 H), 3.75 (m, 1 H), 2.89 (m, 1 H), 1.24 (m, 18 H), 0.91 (s, 9 H), 0.88 (s, 9 H), 0.81 (s, 9 H), 0.09 and 0.08 (2 s, 6 H), 0.05 and 0.04 (2 s, 6 H), -0.02 (s, 3 H), -0.08 (s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) δ 165.66 (C), 154.27 (C), 153.52 (C), 151.26 (C), 145.11 (CH), 137.50 (C), 131.03 (C), 128.49 (CH), 127.86 (2 CH), 123.97 (CH), 105.21 (C), 90.04 (CH), 84.93 (CH), 76.31 (CH), 72.97 (CH2), 71.07 (CH), 64.00 (CH2), 62.37 (CH2), 34.24 (CH), 29.65 (CH), 26.20 (CH3), 25.84 (CH3), 25.77 (CH3), 24.57 (CH3), 24.42 (CH3), 23.49 (CH3), 18.66 (C), 18.04 (C), 17.95 (C), -4.19 (CH3), -4.68 (CH3), -4.88 (CH3), -4.90 (CH3), -5.18 (CH3), -5.44 (CH3). Example 50 [0125] 3-N-(2,4,6-triisopropylbenzenesulfonyl)-2′,3′,5′-tris- O-(tert- butyldimethylsilyl)-1-α-D-ribofuranosyl-5-[(benzyloxy)methy l]uracil (VAL-1-123 was prepared by the following procedure and with the following results: Treatment of 5- [(benzyloxy)methyl]-2′,3′,5′-tris-O-(tert-butyldimethy lsilyl)uridine (97 mg, 0.137 mmol) afforded 123 mg of product (92%). ¹ H NMR (400 MHz, Chloroform-d) δ 8.28 (s, 1 H), 7.49 (m, 4 H), 7.44 (m, 1 H), 7.31 (s, 2 H), 6.23 (d, 1 H, J = 3.5 Hz), 4.76 (s, 2 H), 4.70 (m, 1 H), 4.48 (AB d, 1 H, J = 14.6 Hz), 4.44 (AB d, 1 H, J = 14.6 Hz), 4.41 (m, 1 H), 4.10 (sep, 2 H, J = 6.6 Hz), 3.91 (q, 1 H, J = 5.2 Hz), 3.84 (AB dd, 1 H, J = 10.8, 5.0 Hz), 3.64 (AB dd, 1 H, J = 10.8, 5.0 Hz), 3.03 (sep, 1 H, J = 6.9 Hz), 1.37 (d, 6 H, J = 7.1 Hz), 1.34 (d, 12 H, J = 6.6 Hz), 1.00 (s, 9 H), 0.96 (s, 9 H), 0.91 (s, 9 H), 0.17 (s, 3 H), 0.14 (s, 3 H), 0.10 (s, 3 H), 0.08 (s, 3 H), 0.04 (s, 3 H), -0.11 (s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) δ 161.21 (C), 155.00 (C), 151.99 (C), 147.65 (C), 137.67 (C), 132.59 (CH), 130.18 (C), 128.55 (CH), 127.91 (CH), 127.67 (CH), 124.23 (CH), 112.31 (C), 88.58 (CH), 83.95 (CH), 72.92 (CH2), 71.99 (CH), 71.44 (CH), 64.50 (CH2), 62.97 (CH2), 34.30 (CH), 29.34 (CH), 25.97 (CH3), 25.91 (CH3), 25.75 (CH3), 24.55 (CH3), 24.51 (CH3), 23.50 (CH3), 23.46 (CH3),18.40 (C), 18.02 (C), 17.89 (C), -4.28 (CH3), - 4.47 (CH3), -4.76 (CH3), -4.95 (CH3), -5.31 (CH3), -5.33 (CH3). Example 51 [0126] 3-N-(2,4,6-triisopropylbenzenesulfonyl)-2′,3′,5′-tris- O-(tert- butyldimethylsilyl)-1-α-D-ribofuranosyl-5-[{2-chloro(benzyl oxy)}methyl]uracil (VAL-2- 22F1 was prepared by the following procedure and with the following results: Treatment of 5-[(benzyloxy)methyl]-2′,3′,5′-tris-O-(tert-butyldimet hylsilyl)uridine (144 mg, 0.165 mmol) afforded 151 mg of product (91%). ¹ H NMR (400 MHz, Chloroform-d) δ 8.22 (br t, 1 H, J = 1.1 Hz), 7.51 (m, 1 H), 7.39 (m, 1 H), 7.31 (m, 1 H), 7.28 (m, 1 H), 7.20 (s, 2 H), 6.14 (d, 1 H, J = 4.0 Hz), 4.74 (s, 2 H), 4.61 (dd, 1 H, J = 5.2, 4.0 Hz), 4.46 (AB dd, 1 H, J = 13.4, 1.2 Hz), 4.42 (AB dd, 1 H, J = 13.4, 1.0 Hz), 4.32 (t, 1 H, J = 5.2 Hz), 4.00 (sep, 2 H, J = 6.8 Hz), 3.81 (q, 1 H, J = 5.2 Hz), 3.75 (AB dd, 1 H, J = 11.0, 5.2 Hz), 3.55 (AB dd, 1 H, J = 11.0, 5.2 Hz), 2.92 (sep, 1 H, J = 6.9 Hz), 1.26 (d, 6 H, J = 6.9 Hz), 1.24 (d, 6 H, J = 6.8 Hz), 1.23 (d, 6 H, J = 6.8 Hz), 0.90 (s, 9 H), 0.86 (s, 9 H), 0.80 (s, 9 H), 0.07 (s, 3 H), 0.04 (s, 3 H), 0.00 (s, 3 H), -0.02 (s, 3 H), -0.06 (s, 3 H), -0.21 (s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) δ 161.18 (C), 155.02 (C), 152.01 (C), 147.65 (C), 135.41 (C), 133.01 (C), 132.78 (CH), 130.15 (C), 129.42 (CH), 128.98 (CH), 128.97 (CH), 126.93 (CH), 124.23 (CH), 112.07 (C), 88.62 (CH), 83.96 (CH), 71.90 (CH), 71.43 (CH), 70.02 (CH2), 65.11 (CH2), 62.95 (CH2), 34.30 (CH), 29.35 (CH), 25.97 (CH3), 25.91 (CH3), 25.75 (CH3), 24.53 (CH3), 24.50 (CH3), 23.50 (CH3), 23.46 (CH3),18.40 (C), 18.02 (C), 17.89 (C), -4.29 (CH3), -4.47 (CH3), -4.76 (CH3), -4.95 (CH3), -5.31 (CH3), -5.33 (CH3). Example 52 [0127] 5-[(tert-butyldimethylsilyloxy)methyl]-4-O-(2,4,6- triisopropylbenzenesulfonyl)-2′,3′,5′-tris-O-(tert-but yldimethylsilyl)uridine (VAL-1-137 was prepared by the following procedure and with the following results: Treatment of 5- [(tert-butyldimethylsilyloxy)methyl]-2′,3′,5′-tris-O-( tert-butyldimethylsilyl)uridine (195 mg, 0.267 mmol) afforded 120 mg of product (45%). ¹ H NMR (400 MHz, Chloroform-d) δ 7.86 (s, 1 H), 7.07 (s, 2 H), 5.76 (d, 1 H, J = 4.4 Hz), 4.36 (s, 2 H), 4.15 (sep, 2 H, J = 6.7 Hz), 3.98 (m, 2 H), 3.83 (t, 1 H, J = 4.4 Hz), 3.77 (AB dd, 1 H, J = 11.4, 3.5 Hz), 3.64 (AB dd, 1 H, J = 11.4, 3.4 Hz), 2.78 (sep, 1 H, J = 6.9 Hz), 1.16 (m, 18 H), 0.81 (s, 9 H), 0.80 (s, 9 H), 0.77 (s, 9 H), 0.70 (s, 9 H), 0.03 (s, 3 H), 0.02 (s, 3 H), 0.00 (s, 3 H), -0.01 (s, 3 H), -0.05 (s, 3 H), -0.06 (s, 3 H), -014 (s, 3 H), -0.21 (s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) δ 165.35 (C), 154.25 (C), 153.57 (C), 151.10 (C), 144.25 (CH), 131.23 (C), 123.96 (CH), 107.84 (C), 90.31 (CH), 85.05 (CH), 75.97 (CH), 71.53 (CH), 62.90 (CH2), 57.62 (CH2), 34.24 (C), 29.64 (CH), 26.15 (CH3), 25.88 (CH3), 25.84 (CH3), 25.77 (CH3), 24.58 (CH3), 24.40 (CH3), 23.49 (CH3), 18.58 (C), 18.27 (C), 18.03 (C), 17.95 (C), -4.25 (CH3), -4.74 (CH3), -4.83 (CH3), -4.88 (CH3), -5.08 (CH3), -5.31 (CH3), -5.33 (CH3), -5.46 (CH3). Examples 53 – 61: synthesis of 5-modified-4-N-hydroxy-2′,3′,5′-tris-O-(tert- butyldimethylsilyl)cytosines [0128] General procedure for the synthesis of 5-modified-4-N-hydroxy-2′,3′,5′-tris- O-(tert-butyldimethylsilyl)cytosines. A 5-modified-4-O-(2,4,6- triisopropylbenzenesulfonyl)-2′,3′,5′-tris-(tert-butyl dimethylsilyl)uridine was dissolved in anhydrous acetonitrile under nitrogen atmosphere to achieve concentration ranging from 20 to 100 mM. Hydroxylamine hydrochloride (4.0 to 8.0 eq) and triethylamine (4.0 to 8.0 eq) were added. The reaction mixture was stirred at room temperature for the period from 14 to 18 h. The solvent was evaporated, and the residue was applied onto a chromatography column (SiO2, Hexanes/ EtOAc = 4:1) to afford the product as a white waxy solid. Example 53 [0129] 5-[1-phenyl-2,2-(dimethyl)propoxymethyl]-4-N-hydroxy-2′,3� ��,5′-tris-O-(tert- butyldimethylsilyl)cytosine (VAL-1-80 was prepared by the following procedure and with the following results: Treatment of 5-[1-phenyl-2,2-(dimethyl)propoxymethyl]-4-O-(2,4,6- triisopropylbenzenesulfonyl)-2′,3′,5′-tris-O-(tert-but yldimethylsilyl)uridine (205 mg, 0.200 mmol) afforded 157 mg of product (100%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 8.25 (br s, 1 H), 7.21 (m, 5 H), 6.78 and 6.76 (2 s, 1 H), 5.90 and 5.89 (2 d, 1 H, J = 7.0 Hz), 4.05 (m, 3 H), 3.96 (m, 2 H), 3.82 and 3.78 (2 d, 1 H, J = 12.9 and 12.8 Hz), 3.67 (m, 2 H), 0.88 (s, 9 H), 0.86 (s, 9 H), 0.83 (s, 18 H), 0.06 and 0,05 (2 s, 6 H), 0.04, 0.02 and 0.01 (3 s, 6 H), -0.01 and -0.02 (3 s, 3 H), -0.04 and -0.05 (3 s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 149.25 (C), 143.61 and 143.54 (C), 139.17 and 139.11 (C), 128.79 and 128.73 (CH), 128.35 (CH), 127.60 and 127.55 (CH), 127.38 and 127.33 (CH), 108.52 and 108.33 (C), 89.94 and 89.53 (CH), 87.54 (CH), 85.32 and 85.23 (CH), 73.88 and 73.64 (CH), 72.69 and 72.61 (CH), 63.68 (CH2), 63.59 (CH2), 35.67 and 35.60 (C), 26.38 and 26.36 (CH3), 26.02 and 25.99 (CH3), 25.87 (CH3), 25.77 (CH3), 18.46 and 18.41 (C), 18.10 (C), 17.99 (C), -4.36 and -4.42 (CH3), -4.47 (CH3), -4.62 (CH3), -4.67 and -4.78 (CH3), -5.32 (CH3), -5.36 and -5.38 (CH3). Example 54 [0130] 5-[1-(2-methyl)phenyl-2,2-(dimethyl)propoxymethyl]-4-N-hydro xy-2′,3′,5′- tris-O-(tert-butyldimethylsilyl)cytosine (VAL-1-95 was prepared by the following procedure and with the following results: Treatment of 5-[1-(2-methyl)phenyl-2,2- (dimethyl)propoxymethyl]-4-O-(2,4,6-triisopropylbenzenesulfo nyl)-2′,3′,5′-tris-O-(tert- butyldimethylsilyl)uridine (47 mg, 0.045 mmol) afforded 35 mg of product (98%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 7.35 (br m, 1 H), 7.14 (m, 3 H), 6.85 and 6.78 (2 s, 1 H), 5.98 and 5.92 (2 d, 1 H, J = 6.5 Hz), 4.35 and 4.33 (2 s, 1 H), 4.12 (m, 4 H), 3.99 (m, 1 H), 3.72 (m, 2 H), 2.32 (s, 3 H), 0.94, 0.93, 0.91, 0.88, 0.87, 0.86 (6 s, 36 H), 0.10 and 0.09 (2 s, 9 H), 0.06 and 0.04 (2 s, 3 H), 0.03 and 0.01 (2 s, 3 H), -0.02 (s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 149.19 and 149.14 (C), 143.71 (C), 143.52 (C), 137.07 and 136.85 (C), 130.20 (CH), 128.82 and 128.44 (CH), 127.86 (CH), 127.03 and 126.97 (CH), 125.40 and 125.21 (CH), 108.66 and 108.31 (C), 87.49 and 87.24 (CH), 85.49 and 85.22 (CH), 84.38 and 84.20 (CH), 74.00 and 73.17 (CH), 72.79 and 72.63 (CH), 63.71 and 63.67 (CH2), 63.51 and 63.16 (CH2), 36.96 and 36.81 (C), 26.43 (CH3), 26.04 and 25.96 (CH3), 25.85 (CH3), 25.76 (CH3), 20.43 (CH3), 18.47 and 18.36 (C), 18.09 (C), 17.97 and 17.96 (C), -4.41 (CH3), -4.47 and -4.48 (CH3), -4.61 (CH3), -4.76 and -4.82 (CH3), -5.32 (CH3), -5.40 and -5.43 (CH3). Example 55 [0131] 5-[1-(2-chloro)phenyl-2,2-(dimethyl)propoxymethyl]-4-N-hydro xy-2′,3′,5′- tris-O-(tert-butyldimethylsilyl)cytosine (VAL-1-105 was prepared by the following procedure and with the following results: Treatment of 5-[1-(2-chloro)phenyl-2,2- (dimethyl)propoxymethyl]-4-O-(2,4,6-triisopropylbenzenesulfo nyl)-2′,3′,5′-tris-O-(tert- butyldimethylsilyl)uridine (21 mg, 0.020 mmol) afforded 17 mg of product (100%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 7.46 (d, 1 H, J = 7.6 Hz), 7.27 (m, 1 H), 7.21 (m, 2 H), 7.19 (m, 2 H), 6.87 and 6.85 (2 s, 1 H), 5.96 and 5.92 (2 d, 1 H, J = 6.5 Hz), 4.64 and 4.61 (2 s, 1 H), 4.07 (m, 5 H), 3.77 (m, 2 H), 0.95 and 0.93 (2 s, 18 H), 0.88 and 0.87 (2 s, 18 H), 0.11 (s, 3 H), 0.10 (s, 6 H), 0.08 and 0.05 (2 s, 3 H), 0.04 and 0.03 (2 s, 3 H), 0.01 and -0.02 (2 s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 148.97 and 148.90 (C), 143.83 and 143.76 (C), 137.33 and 137.22 (C), 134.88 and 134.62 (CH), 129.89 and 129.75 (CH), 129.25 and 129.20 (CH), 128.48 and 128.44 (CH), 126.30 and 126.16 (CH), 124.06 and 123.78 (C), 107.78 and 107.54 (C), 87.55 (CH), 85.48 and 85.26 (CH), 84.05 and 83.22 (CH), 74.16 and 74.01 (CH), 72.70 and 72.45 (CH), 64.32 and 63.70 (CH2), 63.59 and 63.45 (CH2), 36.85 and 36.77 (C), 26.10 and 26.04 (CH3), 25.96 (CH3), 25.85 (CH3), 25.75 (CH3), 18.48 and 18.38 (C), 18.09 (C), 17.96 (C), -4.44 (CH3), -4.45 and -4.67 (CH3), -4.63 (CH3), -4.81 (CH3), -5.31 (CH3), -5.40 (CH3). Example 56 [0132] 5-[1-phenyl-1-(cyclohexyl)methoxymethyl]-4-N-hydroxy-2′,3� ��,5′-tris-O-(tert- butyldimethylsilyl)cytosine (VAL-1-86 was prepared by the following procedure and with the following results: Treatment of 5-[1-phenyl-1-(cyclohexyl)methoxymethyl]-4-O- (2,4,6-triisopropylbenzenesulfonyl)-2′,3′,5′-tris-O-(t ert-butyldimethylsilyl)uridine (59 mg, 0.056 mmol) afforded 14 mg of product (30%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 9.86 and 9.82 (2 br s, 1 H), 8.27 and 8.25 (2 br s, 1 H), 7.24 (m, 5 H), 6.78 (s, 1 H), 5.90 and 5.88 (2 d, 1 H, J = 6.6 Hz), 4.92 (m, 1 H), 4.39 (m, 1 H), 4.02 (m, 6 H), 3.84 (m, 2 H), 2.00 (m, 1 H), 1.65 (m, 8 H), 1.61 (m, 2 H), 0.92 (s, 18 H), 0.88 and 0.86 (2 s, 9 H), 0.11, 0.10, 0.09, and 0.08 (4 s, 6 H), 0.06, 0.05, 0.04, and 0.03 (4 s, 6 H), 0.00 and -0.02 (2 s, 3 H), -0.05 and -0.06 (2 s, 3 H). Example 57 [0133] 5-[1-(phenyl)ethoxymethyl]-4-N-hydroxy-2′,3′,5′-tris-O -(tert- butyldimethylsilyl)cytosine (VAL-1-155 was prepared by the following procedure and with the following results: Treatment of 5-[1-(phenyl)ethoxymethyl]-4-O-(2,4,6- triisopropylbenzenesulfonyl)-2′,3′,5′-tris-O-(tert-but yldimethylsilyl)uridine (29 mg, 0.029 mmol) afforded 14 mg of product (20%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 7.34 (m, 4 H), 7.22 (m, 1 H), 6.88 and 6.85 (2 s, 1 H), 5.93 and 5.91 (2 d, 1 H, J = 6.5 Hz), 4.47 (2 q, 1 H, J = 6.4 Hz), 4.02 (m, 5 H), 3.74 (m, 2 H), 1.45 and 1.44 (2 d, 3 H, J = 6.4 Hz), 0.93 (s, 9 H), 0.90 (s, 9 H), 0.88 and 0.87 (2 s, 9 H), 0.10 and 0.09 (2 s, 6 H), 0.08 and 0.03 (2 s, 3 H), 0.06 and 0.04 (2 s, 6 H), 0.01 and 0.00 (2 s, 3 H). Example 58 [0134] 5-[(1-phenyl)propoxymethyl]-4-N-hydroxy-2′,3′,5′-tris- O-(tert- butyldimethylsilyl)cytosine (VAL-2-15 was prepared by the following procedure and with the following results: Treatment of 5-[(1-phenyl)propoxymethyl]-4-O-(2,4,6- triisopropylbenzenesulfonyl)-2′,3′,5′-tris-O-(tert-but yldimethylsilyl)uridine (75 mg, 0.075 mmol) afforded 49 mg of product (88%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 7.24 (m, 5 H), 6.92 and 6.87 (2 s, 1 H), 5.89 and 5.88 (2 d, 1 H, J = 6.4 Hz), 4.20 (m, 1 H), 4.07 (m, 2 H), 4.02 (m, 2 H), 3.96 (m, 1 H), 3.71 (m, 2 H), 1.81 (m, 1 H), 1.62 (m, 1 H), 0.89 and 0.88 (2 s, 9 H), 0.85 and 0.84 (2 s, 9 H), 0.84 and 0.82 (2 s, 9 H), 0.80 (m, 3 H), 0.06 and 0.05 (2 s, 6 H), 0.03 and 0.00 (2 s, 6 H), -0.03 and -0.05 (2 s, 6 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 148.67 and 148.61 (C), 144.79 and 144.62 (C), 141.85 and 141.67 (C), 131.07 and 130.95 (CH), 128.40 (CH), 127.68 and 127.62 (CH), 126.93 and 126.83 (CH), 107.21 and 107.00 (C), 87.84 and 87.67 (CH), 85.45 (CH), 84.00 and 83.18 (CH), 74.27 (CH), 72.48 and 72.40 (CH), 63.61 (CH2), 63.32 (CH2), 30.96 and 30.90 (CH2), 26.03 and 25.98 (CH3), 25.84 (CH3), 25.75 (CH3), 18.45 and 18.42 (C), 18.09 (C), 17.95 (C), 10.28 and 10.24 (CH3), -4.44 (CH3), -4.66 (CH3), -4.67 (CH3), -4.76 (CH3), -5.33 (CH3), -5.38 (CH3). Example 59 [0135] 5-[(1-phenyl-2-methyl)propoxymethyl]-4-N-hydroxy-2′,3′,5 ′-tris-O-(tert- butyldimethylsilyl)cytosine (VAL-2-43) was prepared by the following procedure and with the following results: Treatment of 5-[(1-phenyl-2-methyl)propoxymethyl]-4-O-(2,4,6- triisopropylbenzenesulfonyl)-2′,3′,5′-tris-O-(tert-but yldimethylsilyl)uridine (53 mg, 0.052 mmol) afforded 20 mg of product (50%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 7.24 (m, 7 H), 6.83 and 6.80 (2 s, 1 H), 5.90 and 5.89 (2 d, 1 H, J = 6.5 and 6.6 Hz), 4.09 (m, 1 H), 3.97 (m, 5 H), 3.73 (AB d, 1 H, J = 12.0 Hz), 3.69 (AB d, 1 H, J = 12.0 Hz), 1.89 (m, 1 H), 0.94 (m, 3 H), 0.89 (s, 9 H), 0.87, 0.85, 0.84 and 0.83 (4 s, 18 H), 0.69 and 0.68 (2 d, 3 H, J = 6.8 Hz), 0.07 and 0.06 (2 s, 6 H), 0.05 and 0.01 (2 s, 3 H), 0.03 (s, 3 H), 0.01 and -0.01 (2 s, 6 H), -0.03 (s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 149.02 (C), 144.00 and 142.90 (C), 140.83 and 140.73 (C), 129.60 and 129.51 (CH), 128.14 and 128.12 (CH), 127.53 and 127.48 (CH), 127.45 and 127.42 (CH), 108.09 and 107.87 (C), 87.99 and 87.74 (CH), 87.52 and 87.27 (CH), 83.32 (CH), 74.03 and 73.88 (CH), 72.56 and 72.52 (CH), 63.75 and 63.41 (CH2), 63.51 (CH2), 34.83 and 34.81 (CH), 26.03 and 25.98 (CH3), 25.85 (CH3), 25.76 (CH3), 19.11 and 19.06 (CH3), 19.03 and 19.01 (CH3), 18.46 and 18.41 (C), 18.09 (C), 17.97 (C), -4.39 and -4.43 (CH3), -4.45 and -4.47 (CH3), -4.63 and -4.65 (CH3), -4.69 and -4.77 (CH3), -5.32 (CH3), -5.38 (CH3). Example 60 [0136] 5-[(benzyloxy)methyl]-4-N-hydroxy-2′,3′,5′-tris-O-(ter t- butyldimethylsilyl)cytosine (VAL-1-129) was prepared by the following procedure and with the following results: Treatment of 5-[(benzyloxy)methyl]-4-O-(2,4,6- triisopropylbenzenesulfonyl)-2′,3′,5′-tris-O-(tert-but yldimethylsilyl)uridine (22 mg, 0.023 mmol) afforded 17 mg of product (100%). ¹ H NMR (400 MHz, Chloroform-d) δ 8.17 (br s, 1 H), 7.50 (br s, 1 H), 7.29 (m, 5 H), 6.98 (s, 1 H), 5.97 (d, 1 H, J = 6.8 Hz), 4.53 (s, 2 H), 4.17 (s, 2 H), 4.12 (m, 1 H), 4.06 (m, 1 H), 3.98 (m, 1 H), 3.85 (AB dd, 1 H, J = 11.2, 2.6 Hz), 3.74 (AB dd, 1 H, J = 11.2, 2.0 Hz), 0.91 (s, 18 H), 0.87 (s, 9 H), 0.09 (s, 3 H), 0.08 (s, 3 H), 0.07 (s, 6 H), 0.03 (s, 3 H), -0.01 (s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) δ 151.50 (C), 149.30 (C), 138.10 (C), 130.01 (CH), 128.40 (CH), 127.80 (CH), 127.72 (CH), 107.59 (C), 87.09 (CH), 85.60 (CH), 74.21 (CH), 72.53 (CH2), 72.50 (CH), 65.02 (CH2), 63.35 (CH2), 26.06 (CH3), 25.84 (CH3), 25.75 (CH3), 18.50 (C), 18.09 (C), 17.95 (C), -4.38 (CH3), -4.46 (CH3), -4.65 (CH3), -4.72 (CH3), -5.36 (CH3), -5.42 (CH3). Example 61 [0137] 5-[(tert-butyldimethylsilyloxy)methyl]-4-N-hydroxy-2′,3′ ,5′-tris-O-(tert- butyldimethylsilyl)cytosine (VAL-1-138 was prepared by the following procedure and with the following results: Treatment of 5-[(tert-butyldimethylsilyloxy)methyl]-4-O-(2,4,6- triisopropylbenzenesulfonyl)-2′,3′,5′-tris-O-(tert-but yldimethylsilyl)uridine (144 mg, 0.145 mmol) afforded 108 mg of product (100%). ¹ H NMR (400 MHz, Chloroform-d) δ 8.25 (br s, 1 H), 6.80 (s, 1 H), 5.91 (d, 1 H, J = 6.5 Hz), 4.32 (s, 2 H), 4.12 (m, 1 H), 4.07 (m, 1 H), 3.96 (m, 1 H), 3.73 (AB dd, 1 H, J = 10.8, 3.8 Hz), 3.66 (AB dd, 1 H, J = 10.8, 6.0 Hz), 0.91 (2 s, 27 H), 0.86 (s, 9 H), 0.09 (s, 18 H), 0.02 (s, 3 H), -0.02 (s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) δ 151.50 (C), 149.28 (C), 143.59 (C), 127.97 (CH), 110.34 (C), 87.86 (CH), 85.01 (CH), 73.48 (CH), 72.52 (CH), 63.62 (CH2), 57.88 (CH2), 26.02 (CH3), 25.92 (CH3), 25.85 (CH3), 25.76 (CH3), 18.45 (C), 18.32 (C), 18.07 (C), 17.97 (C), -4.45 (CH3), -4.49 (CH3), -4.61 (CH3), -4.77 (CH3), -5.31 (CH3), -5.35 (CH3). Examples 62 – 68: synthesis of 5-modified-2′,3′,5′-tris-(tert-butyldimethylsilyl)cyto sines [0138] General procedure for the synthesis of 5-modified-2′,3′,5′-tris-(tert- butyldimethylsilyl)cytosines. A 5-modified-4-O-(2,4,6-triisopropylbenzenesulfonyl)- 2′,3′,5′-tris-(tert-butyldimethylsilyl)uridine was dissolved in anhydrous 1,4-dioxane under nitrogen atmosphere to achieve concentration ranging from 20 to 70 mM. A solution of ammonia in methanol (7 M, 16.0 to 40.0 eq) was added. The reaction mixture was sealed in a thick wall tube, immersed into a pre-heated oil bath, and stirred at the temperature ranging from +90 to +110 ºC for the period from 14 to 24 h. The solvent was evaporated, and the residue was applied onto a chromatography column (SiO2, Dichloromethane/Methanol eluting from 1:0 to 20:1) to afford the product as a white waxy solid. Example 62 [0139] 5-[1-phenyl-2,2-(dimethyl)propoxymethyl]-2′,3′,5′-tris -O-(tert- butyldimethylsilyl)cytosine (VAL-1-83 was prepared by the following procedure and with the following results: Treatment of 5-[1-phenyl-2,2-(dimethyl)propoxymethyl]-4-O-(2,4,6- triisopropylbenzenesulfonyl)-2′,3′,5′-tris-O-(tert-but yldimethylsilyl)uridine (219 mg, 0.213 mmol) afforded 130 mg of product (80%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 7.29 (m, 4 H), 7.21 (m, 2 H), 5.92 and 5.91 (2 d, 1 H, J = 5.0 and 4.9 Hz), 4.15 (m, 2 H), 4.01 (m, 1 H), 3.93 (m, 3 H), 3.84 (m, 1 H), 3.65 (m, 1 H), 0.88, 0.87, and 0.86 (3 s, 27 H), 0.83 and 0.80 (2 s, 9 H), 0.06 and 0.05 (2 s, 3 H), 0.04 and 0.03 (2 s, 6 H), 0.03 and 0.02 (2 s, 3 H), 0.00 and -0.04 (2 s, 3 H), -0.05 and -0.07 (2 s, 3 H). val ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 165.36 and 165.31 (C), 155.66 and 155.62 (C), 140.02 and 139.84 (CH), 138.51 and 138.47 (C), 128.37 and 128.29 (CH), 128.00 and 127.92 (CH), 127.82 and 127.77 (CH), 103.01 and 102.83 (C), 89.95 (CH), 89.40 and 89.33 (CH), 84.54 and 84.40 (CH), 75.56 and 75.53 (CH), 71.62 and 71.57 (CH), 66.26 and 66.91 (CH2), 62.92 and 62.81 (CH2), 35.52 and 35.46 (C), 26.43 (CH3), 26.08 and 26.05 (CH3), 25.89 (CH3), 25.88 (CH3), 18.52 and 18.46 (C), 18.07 and 18.06 (C), 18.03 and 18.01 (C), -4.28 (CH3), -4.36 and - 4.49 (CH3), -4.78 (CH3), -4.82 and -4.84 (CH3), -5.22 and -5.29 (CH3), -5.32 and -5.40 (CH3). Example 63 [0140] 5-[1-(2-methyl)phenyl-2,2-(dimethyl)propoxymethyl]-2′,3′ ,5′-tris-O-(tert- butyldimethylsilyl)cytosine (VAL-1-96) was prepared by the following procedure and with the following results: Treatment of 5-[1-(2-methyl)phenyl-2,2-(dimethyl)propoxymethyl]- 4-O-(2,4,6-triisopropylbenzenesulfonyl)-2′,3′,5′-tris- O-(tert-butyldimethylsilyl)uridine (39 mg, 0.037 mmol) afforded 25 mg of product (85%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 7.35 (m, 2 H), 7.14 (m, 3 H), 6.85 and 6.78 (2 s, 1 H), 5.98 and 5.92 (2 d, 1 H, J = 4.8 Hz), 4.36 and 4.31 (2 s, 1 H), 4.14 (m, 1 H), 4.03 (m, 2 H), 3.94 (m, 3 H), 3.67 (m, 1 H), 2.33 and 2.26 (2 s, 3 H), 0.94 and 0.91 (2 d, 9 H), 0.89, 0.87, 0.86, and 0.81 (4 s, 27 H), 0.09, 0.06, 0.05, 0.04, 0.03, and 0.00 (5 s, 15 H), -0.03 and -0.07 (2 s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 164.92 (C), 155.59 and 155.58 (C), 140.18 and 139.94 (CH), 137.30 and 137.04 (C), 136.86 and 136.69 (C), 130.50 (CH), 127.54 and 127.59 (CH), 127.34 (CH), 125.92 and 125.73 (CH), 103.16 and 102.70 (C), 89.65 and 89.01 (CH), 84.82 and 84.36 (CH), 84.65 and 82.88 (CH), 75.90 and 75.72 (CH), 71.78 and 71.32 (CH), 66.41 and 65.31 (CH2), 62.87 and 62.50 (CH2), 36.79 and 36.60 (C), 26.44 and 26.40 (CH3), 26.13 (CH3), 26.04 (CH3), 25.86 (CH3), 20.40 and 20.30 (CH3), 18.54 and 18.42 (C), 18.07 and 18.03 (C), 18.00 (C), -4.23 and -4.29 (CH3), -4.44 and -4.57 (CH3), -4.80 (CH3), - 4.84 (CH3), -5.19 (CH3), -5.32 and -5.41 (CH3). Example 64 [0141] 5-[1-(2-chloro)phenyl-2,2-(dimethyl)propoxymethyl]-2′,3′ ,5′-tris-O-(tert- butyldimethylsilyl)cytosine (VAL-1-107 was prepared by the following procedure and with the following results: Treatment of 5-[1-(2-chloro)phenyl-2,2- (dimethyl)propoxymethyl]-4-O-(2,4,6-triisopropylbenzenesulfo nyl)-2′,3′,5′-tris-O-(tert- butyldimethylsilyl)uridine (22 mg, 0.021 mmol) afforded 17 mg of product (100%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 7.55 and 7.53 (2 s, 1 H), 7.54 (m, 1 H), 7.46 and 7.44 (2 s, 1 H), 7.38 (m, 1 H), 7.35 (m, 1 H), 6.04 and 6.00 (2 d, 1 H, J = 4.6 Hz), 4.76 and 4.73 (2 s, 1 H), 4.23 (m, 3 H), 4.03 (m, 3 H), 3.78 (m, 1 H), 1.04 and 1.03 (2 s, 9 H), 0.99, 0.98, 0.96, and 0.92 (4 s, 27 H), 0.18 and 0.17 (2 s, 3 H), 0.12 (m, 12 H), 0.07 and 0.05 (2 s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 165.09 and 165.02 (C), 155.57 (C), 149.14 (C), 140.61 and 140.06 (CH), 136.60 and 135.17 (C), 129.62 and 129.54 (CH), 129.00 and 128.93 (CH), 126.78 and 126.59 (CH), 123.66 (CH), 102.51 and 102.32 (C), 89.58 and 89.39 (CH), 84.61 and 84.27 (CH), 84.15 and 83.38 (CH), 75.89 and 75.78 (CH), 71.56 and 71.30 (CH), 66.61 and 66.10 (CH2), 62.72 (CH2), 36.66 and 36.58 (C), 26.15 (CH3), 26.11 (CH3), 26.05 (CH3), 25.88 (CH3), 18.54 (C), 18.48 (C), 18.07 and 18.02 (C), -4.20 and - 4.26 (CH3), -4.36 and -4.50 (CH3), -4.83 (CH3), -4.88 (CH3), -5.18 and -5.26 (CH3), -5.32 and -5.41 (CH3). Example 65 [0142] 5-[1-phenyl-1-(cyclohexyl)methoxymethyl]-2′,3′,5′-tris -O-(tert- butyldimethylsilyl)cytosine (VAL-1-87 was prepared by the following procedure and with the following results: Treatment of 5-[1-phenyl-1-(cyclohexyl)methoxymethyl]-4-O- (2,4,6-triisopropylbenzenesulfonyl)-2′,3′,5′-tris-O-(t ert-butyldimethylsilyl)uridine (61 mg, 0.057 mmol) afforded 17 mg of product (38%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 7.46 and 7.43 (2 s, 1 H), 7.34 (m, 3 H), 7.21 (s, 2 H), 5.94 and 5.90 (2 d, 1 H, J = 4.5 Hz), 5.85 (br s, 2 H), 4.15 (m, 2 H), 4.03 (m, 1 H), 3.91 (m, 4 H), 3.69 (m, 1 H), 2.02 (m, 1 H), 1.74 (m, 1 H), 1.62 (m, 2 H), 1.25 (m, 3 H), 1.09 (m, 1 H), 0.89 and 0.88 (2 s, 9 H), 0.88 and 0.87 (2 s, 9 H), 0.85 and 0.82 (2 s, 9 H), 0.08 and 0.06 (2 s, 3 H), 0.05 and 0.04 (2 s, 6 H), 0.04 and 0.02 (2 s, 3 H), 0.00 and - 0.02 (2 s, 3 H), -0.03 and -0.05 (2 s, 3 H). ¹³ C NMR (100 MHz, chloroform-d) for 1:1 mixture of diastereomers δ 165.14 and 165.08 (C), 155.71 and 155.65 (C), 140.27 and 140.03 (CH), 139.95 (C), 128.63 and 128.56 (CH), 128.07 (CH), 127.55 and 127.42 (CH), 102.60 and 102.36 (C), 89.60 and 89.43 (CH), 87.17 and 86.36 (CH), 84.54 and 84.27 (CH), 75.83 and 75.77 (CH), 71.48 and 71.28 (CH), 65.99 and 65.55 (CH2), 62.65 (CH2), 44.02 (CH), 29.78 (CH2), 29.31 (CH2), 26.38 (CH2), 26.13 (CH3), 26.07 (CH3), 25.95 and 25.87 (CH3), 18.58 and 18.50 (C), 18.08 (C), 18.04 and 18.02 (C), -4.23 and -4.25 (CH3), -4.37 (CH3), -4.48 (CH3), -4.86 (CH3), -5.19 and -5.23 (CH3), -5.34 and - 5.41 (CH3). Example 66 [0143] 5-[1-(phenyl)ethoxymethyl]-2′,3′,5′-tris-O-(tert-butyl dimethylsilyl)cytosine (VAL-1-154 was prepared by the following procedure and with the following results: Treatment of 5-[1-(phenyl)ethoxymethyl]-4-O-(2,4,6-triisopropylbenzenesul fonyl)-2′,3′,5′- tris-O-(tert-butyldimethylsilyl)uridine (51 mg, 0.052 mmol) afforded 24 mg of product (64%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 7.56 and 7.54 (2 s, 1 H), 7.32 (m, 5 H), 5.96 and 5.89 (2 d, 1 H, J = 4.2 Hz), 4.44 (m, 1 H), 4.21 and 4.19 (2 d, 1 H, J = 12.2 Hz), 4.09 (m, 3 H), 3.92 (m, 3 H), 3.68 (m, 1 H), 1.48 and 1.46 (2 d, 1 H, J = 6.4 Hz), 0.90 (m, 27 H), 0.06 (m, 18 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 165.16 (C), 155.64 (C), 142.33 and 142.24 (C), 140.13 and 140.03 (CH), 128.91 and 128.85 (CH), 128.17 (CH), 126.28 and 126.16 (CH), 102.44 and 103.36 (C), 89.61 and 89.28 (CH), 84.43 and 84.19 (CH), 77.43 and 76.91 (CH), 75.94 and 75.87 (CH), 71.32 and 71.05 (CH), 65.66 and 65.39 (CH2), 62.57 and 62.44 (CH2), 26.14 and 26.08 (CH3), 26.00 (CH3), 26.87 (CH3), 23.87 (CH3), 18.62 and 18.55 (C), 18.07 (br, C), -4.18 and -4.24 (CH3), -4.35 and -4.47 (CH3), -4.83 and -4.86 (CH3), -5.19 (CH3), -5.35 and -5.38 (CH3), -5.43 and -5.45 (CH3). Example 67 [0144] 5-[(1-phenyl)propoxymethyl]-2′,3′,5′-tris-O-(tert-buty ldimethylsilyl)cytosine (VAL-2-14 was prepared by the following procedure and with the following results: Treatment of 5-[(1-phenyl)propoxymethyl]-4-O-(2,4,6-triisopropylbenzenesu lfonyl)- 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)uridine (63 mg, 0.063 mmol) afforded 28 mg of product (61%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 7.55 and 7.51 (2 s, 1 H), 7.37 (m, 2 H), 7.28 (m, 3 H), 5.91 and 5.85 (2 d, 1 H, J = 4.3 and 4.0 Hz), 4.29 (m, 1 H), 4.18 (m, 1 H), 4.12 (m, 2 H), 4.04 (m, 1 H), 3.88 (AB dd, 1 H, J = 11.5, 2.5 Hz), 3.69 (AB dd, 1 H, J = 11.5, 2.3 Hz), 1.91 (m, 1 H), 1.70 (m, 1 H), 0.86 (m, 27 H), 0.07 and 0.06 (2 s, 6 H), 0.05 and 0.03 (2 s, 6 H), -0.02 and -0.03 (2 s, 3 H), - 0.04 (s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 163.79 and 163.43 (C), 149.12 and 147.42 (C), 141.10 and 140.98 (C), 140.22 and 140.14 (CH), 128.75 and 128.71 (CH), 128.09 (CH), 126.95 and 126.89 (CH), 103.43 and 103.22 (C), 89.65 and 89.56 (CH), 84.58 and 84.45 (CH), 83.81 and 83.13 (CH), 75.75 (CH), 71.34 and 71.11 (CH), 65.29 and 65.07 (CH2), 62.58 and 62.43 (CH2), 30.64 (CH2), 26.11 (CH3), 26.06 (CH3), 25.86 (CH3), 18.56 and 18.53 (C), 18.07 (C), 18.00 (C), 10.28 and 10.26 (CH3), -4.21 and -4.24 (CH3), -4.35 (CH3), -4.45 (CH3), -4.84 and -4.86 (CH3), -5.21 (CH3), -5.40 and -5.45 (CH3). Example 67 [0145] 5-[(1-phenyl-2-methyl)propoxymethyl]-2′,3′,5′-tris-O-( tert- butyldimethylsilyl)cytosine (VAL-2-43F2 was prepared by the following procedure and with the following results: Treatment of 5-[(1-phenyl-2-methyl)propoxymethyl]-4-O- (2,4,6-triisopropylbenzenesulfonyl)-2′,3′,5′-tris-O-(t ert-butyldimethylsilyl)uridine (53 mg, 0.052 mmol) afforded 17 mg of product (44%). ¹ H NMR (400 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 7.48 and 7.45 (2 s, 1 H), 7.34 (m, 4 H), 7.22 (m, 1 H), 5.92 and 5.90 (2 d, 1 H, J = 4.5 and 4.4 Hz), 5.70 and 5.60 (2 br s, 2 H), 4.21 (m, 1 H), 4.12 (m, 1 H), 4.01 (m, 2 H), 3.91 (m, 1 H), 3.79 (AB dd, 1 H, J = 10.8, 4.0 Hz), 3.68 (m, 1 H), 1.98 (m, 1 H), 0.93 (m, 3 H), 0.86 (m, 27 H), 0.02 (m, 18 H). ¹³ C NMR (100 MHz, Chloroform-d) for 1:1 mixture of diastereomers δ 164.76 (C), 151.54 (C), 140.26 and 140.07 (CH), 139.99 (C), 128.60 and 128.54 (CH), 128.08 (CH), 127.50 and 127.40 (CH), 102.68 (C), 89.44 (CH), 87.99 and 87.22 (CH), 84.58 and 84.44 (CH), 76.71 and 76.10 (CH), 71.44 and 71.34 (CH), 65.11 and 63.66 (CH2), 62.73 and 62.65 (CH2), 34.54 (CH), 26.11 and 26.06 (CH3), 25.91 and 25.86 (CH3), 25.80 and 25.79 (CH3), 19.31 and 19.26 (CH3), 19.25 and 18.95 (CH3), 18.56 and 18.50 (C), 18.33 and 18.25 (C), 18.08 and 18.02 (C), -4.24 and -4.39 (CH3), -4.50 and -4.58 (CH3), -4.71 and -4.78 (CH3), -4.82 and -4.85 (CH3), -5.23 and -5.26 (CH3), -5.57 and -5.58 (CH3). Example 68 [0146] 5-[(benzyloxy)methyl]-2′,3′,5′-tris-O-(tert-butyldimet hylsilyl)cytosine (VAL- 1-127 was prepared by the following procedure and with the following results: Treatment of 5-[(benzyloxy)methyl]-4-O-(2,4,6-triisopropylbenzenesulfonyl )-2′,3′,5′-tris- O-(tert-butyldimethylsilyl)uridine (10 mg, 0.011 mmol) afforded 7 mg of product (91%). ¹ H NMR (400 MHz, Chloroform-d) δ 7.72 (s, 1 H), 7.32 (m, 5 H), 5.94 (d, 1 H, J = 4.0 Hz), 5.92 (br s, 2 H), 4.46 (s, 2 H), 4.36 (AB d, 1 H, J = 12.5 Hz), 4.32 (AB d, 1 H, J = 12.5 Hz), 4.15 (t, 1 H, J = 4.2 Hz), 4.07 (m, 1 H), 3.98 (m, 2 H), 3.75 (AB dd, 1 H, J = 11.6, 2.1 Hz), 0.93 (s, 9 H), 0.89 (s, 9 H), 0.88 (s, 9 H), 0.10 (s, 3 H), 0.09 (s, 3 H), 0.09 (s, 3 H), 0.07 (s, 3 H), 0.06 (s, 3 H), 0.05 (s, 3 H). ¹³ C NMR (100 MHz, Chloroform-d) δ 165.00 (C), 155.61 (C), 140.43 (CH), 136.96 (CH), 128.72 (CH), 128.26 (CH), 128.00 (CH), 101.87 (C), 89.49 (CH), 84.27 (CH), 76.01 (CH), 71.71 (CH2), 71.05 (CH), 67.31 (CH2), 62.43 (CH2), 26.23 (CH3), 25.89 (CH3), 25.87 (CH3), 18.70 (C), 18.09 (C), 18.04 (C), -4.20 (CH3), -4.36 (CH3), -4.86 (CH3), -4.99 (2 CH3), -5.35 (CH3). Examples 69 – 89: removal of TBS-protecting groups [0147] General procedure for removal of TBS-protecting groups. A 5-modified- 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)cytosine or its 4-N-hydroxy derivative was dissolved in tetrahydrofurane to achieve concentration ranging from 5 to 40 mM. The solution was immersed in ice-water bath followed by addition of tetra-n-butylammonium hydroxide trihydrate (5.0 to 6.0 eq). The reaction mixture was the period from 10 to 25 h while gradually warming up to room temperature. The solvent was evaporated, and the residue was applied onto a chromatography column (SiO2, EtOAc/Methanol eluting from 1:0 to 100:1 for 4-N-hydroxycytosine and to 20:1 for cytosine derivatives) to afford the product as a glass-like solid. Example 69 [0148] 5-[1-phenyl-2,2-(dimethyl)propoxymethyl]-4-N-(hydroxy)cytidi ne (VAL-1-81 – RIID1258 was prepared by the following procedure and with the following results: Treatment of 5-[1-phenyl-2,2-(dimethyl)propoxymethyl]-4-N-hydroxy-2′,3� ��,5′-tris-O-(tert- butyldimethylsilyl)cytosine (157 mg, 0.200 mmol) afforded 53 mg of product (61%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.25 (m, 5 H), 7.11 and 7.07 (2 s, 1 H), 5.89 and 5.88 (2 d, 1 H, J = 4.3 Hz), 4.16 (m, 2 H), 3.98 (m, 4 H), 3.75 (m, 2 H), 0.91 (s, 9 H). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 151.70 (C), 144.45 (C), 140.69 and 140.65 (C), 129.59 (CH), 129.46 and 129.23 (CH), 128.58 and 128.56 (CH), 128.38 and 128.37 (CH), 110.20 and 110.10 (C), 91.14 and 90.89 (CH), 89.81 and 89.79 (CH), 85.98 and 85.93 (CH), 74.55 (CH), 71.92 and 71.86 (CH), 64.88 and 64.80 (CH2), 63.04 and 62.99 (CH2), 36.51 (C), 26.86 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C21H30N3O7 calculated: 436.20135, observed: 436.19709. Example 70 [0149] 5-[1-phenyl-2,2-(dimethyl)propoxymethyl]cytidine (VAL-1-84 – RIID1259 was prepared by the following procedure and with the following results: Treatment of 5- [1-phenyl-2,2-(dimethyl)propoxymethyl]-2′,3′,5′-tris-O -(tert-butyldimethylsilyl)cytosine (130 mg, 0.171 mmol) afforded 34 mg of product (47%). ¹ H NMR (400 MHz, Methanol- d4) for 1:1 mixture of diastereomers δ 7.89 and 7.81 (2 s, 1 H), 7.29 (m, 5 H), 5.83 and 5.80 (2 d, 1 H, J = 3.0 Hz), 4.18 (m, 3 H), 4.03 (m, 3 H), 3.84 (m, 1 H), 3.70 (m, 1 H), 0.89 and 0.88 (2 s, 9 H). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 166.54 and 166.49 (C), 158.17 and 158.05 (C), 142.49 and 142.30 (CH), 140.40 and 140,00 (C), 129.72 and 129.61 (CH), 128.85 and 128.75 (CH), 128.68 and 128.55 (CH), 105.24 and 104.95 (C), 92.28 and 92.19 (CH), 90.73 and 89.88 (CH), 85.86 and 85.67 (CH), 76.27 and 76.18 (CH), 70.81 and 70.41 (CH), 66.57 and 65.85 (CH2), 62.00 and 61.74 (CH2), 36.44 and 36.34 (C), 26.82 and 26.78 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C21H30N3O6 calculated: 420.21346, observed: 420.22030. Example 71 [0150] 5-[1-(2-methyl)phenyl-2,2-(dimethyl)propoxymethyl]-4-N-(hydr oxy)cytidine (VAL-1-97 – RIID1264 was prepared by the following procedure and with the following results: Treatment of 5-[1-(2-methyl)phenyl-2,2-(dimethyl)propoxymethyl]-4-N-hydro xy- 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)cytosine (35 mg, 0.044 mmol) afforded 11 mg of product (56%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.39 (br m, 1 H), 7.14 (m, 3 H), 7.07 and 7.06 (2 s, 1 H); 5.89 and 5.86 (2 d, 1 H, J = 5.6 Hz), 4.44 (s, 1 H), 4.14 (m, 2 H), 3.87 (m, 3 H), 3.70 (m, 2 H), 2.35 (s, 3 H), 0.94 (s, 9 H). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 151.72 (C), 144.45 (C), 139.20 (C), 138.36 and 138.26 (C), 131.19 (CH), 129.31 and 129.16 (CH), 129.05 (CH), 128.13 and 128.10 (CH), 126.34 and 126.28 (CH), 110.32 and 110.29 (C), 89.77 (CH), 86.03 (CH), 85.15 (br CH), 74.53 (CH), 71.96 (CH), 64.64 and 64.42 (CH2), 63.07 (CH2), 37.81 and 37.78 (C), 26.92 (CH3), 20.64 and 19.34 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C22H32N3O7 calculated: 450.22403, observed: 450.22990. Example 72 [0151] 5-[1-(2-methyl)phenyl-2,2-(dimethyl)propoxymethyl]cytidine (VAL-1-100 – RIID1265 was prepared by the following procedure and with the following results: Treatment of 5-[1-(2-methyl)phenyl-2,2-(dimethyl)propoxymethyl]-2′,3′ ,5′-tris-O-(tert- butyldimethylsilyl)cytosine (24 mg, 0.031 mmol) afforded 8 mg of product (61%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.84 and 7.79 (2 s, 1 H); 7.38 (br m, 1 H), 7.17 (m, 3 H), 5.81 and 5.80 (2 d, 1 H, J = 1.5 Hz), 4.40 (s, 1 H), 4.15 (m, 1 H), 4.01 (m, 4 H), 3.82 (m, 1 H), 3.70 (m, 1 H), 2.32 and 2.30 (2 s, 3 H), 0.94 and 0.93 (2 s, 9 H). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 166.58 and 166.55 (C), 158.21 (C), 142.29 (CH), 138.49 (C), 138.43 and 138.30 (C), 131.44 (CH), 129.01 (CH), 128.40 and 128.37 (CH), 126.53 and 126.47 (CH), 105.17 (C), 92.23 and 92.17 (CH), 85.88 and 85.82 (CH), 84.08 and 83.97 (CH), 76.25 and 76.24 (CH), 70.85 and 70.61 (CH), 65.87 (CH2), 62.01 and 61.86 (CH2), 37.64 and 37.60 (C), 26.81 (CH3), 20.02 and 20.64 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C22H32N3O6 calculated: 434.22911, observed: 434.23500. Example 73 [0152] 5-[1-(2-chloro)phenyl-2,2-(dimethyl)propoxymethyl]-4-N-(hydr oxy)cytidine (VAL-1-108 – RIID1271 was prepared by the following procedure and with the following results: Treatment of 5-[1-(2-chloro)phenyl-2,2-(dimethyl)propoxymethyl]-4-N-hydro xy- 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)cytosine (17 mg, 0.021 mmol) afforded 5 mg of product (53%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.52 (m, 1 H), 7.24 (m, 3 H), 7.10 and 7.05 (2 s, 1 H), 5.90 and 5.89 (2 d, 1 H, J = 5.6 Hz), 4.68 and 4.67 (2 s, 1 H), 4.18 (m, 2 H), 3.97 (m, 3 H), 3.78 (m, 2 H), 0.91 and 0.90 (2 s, 9 H). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 152.12 (C), 140.86 and 140.51 (CH), 138.80 (C), 135.86 (C), 131.13 (C), 130.31 (CH), 129.98 (CH), 129.50 (CH), 127.28 (CH), 109.74 and 109.55 (C), 90.76 (CH), 86.45 and 86.40 (CH), 85.35 (CH), 75.72 and 75.69 (CH), 71.49 (CH), 65.37 and 65.16 (CH2), 62.53 and 62.44 (CH2), 37.72 (C), 26.64 and 26.55 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C21H29 ³⁵ ClN3O7 calculated: 470.16940, observed: 470.17352. Example 74 [0153] 5-[1-(2-chloro)phenyl-2,2-(dimethyl)propoxymethyl]cytidine (VAL-1-109 – RIID1272 was prepared by the following procedure and with the following results: Treatment of 5-[1-(2-chloro)phenyl-2,2-(dimethyl)propoxymethyl]-2′,3′ ,5′-tris-O-(tert- butyldimethylsilyl)cytosine (17 mg, 0.021 mmol) afforded 7 mg of product (73%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.90 and 7.76 (2 s, 1 H); 7.50 (m, 1 H), 7.36 (m, 3 H), 5.83 and 5.78 (2 d, 1 H, J = 3.2 Hz), 4.65 and 4.63 (2 s, 1 H), 4.15 (m, 3 H), 4.01 (m, 1 H), 3.88 (m, 3 H), 0.95 (s, 9 H). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 166.51 (C), 158.29 (C), 142.83 and 142.67 (CH), 138.22 and 137.78 (C), 135.98 and 135.85 (C), 130.94 (CH), 130.59 and 130.44 (CH), 130.12 and 129.98 (CH), 127.73 and 127.63 (CH), 104.80 and 104.48 (C), 92.49 and 92.30 (CH), 85.78 and 85.76 (CH), 84.34 and 82.29 (CH), 76.30 and 76.25 (CH), 70.80 and 70.56 (CH), 65.58 (CH2), 61.76 and 61.56 (CH2), 37.64 and 37.51 (C), 26.59 and 26.54 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C21H29 ³⁵ ClN3O6 calculated: 454.17449, observed: 454.18124. Example 75 [0154] 5-[1-phenyl-1-(cyclohexyl)methoxymethyl]-4-N-(hydroxy)cytidi ne (VAL-1- 88 – RIID1262 was prepared by the following procedure and with the following results: Treatment of 5-[1-phenyl-1-(cyclohexyl)methoxymethyl]-4-N-hydroxy-2′,3� ��,5′-tris-O-(tert- butyldimethylsilyl)cytosine (14 mg, 0.311 mmol) afforded 2 mg of product (22%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.32 (m, 2 H), 7.26 (m, 3 H), 7.10 and 7.07 (2 s, 1 H), 5.87 (d, 1 H, J = 4.5 Hz), 4.12 (m, 1 H), 4.00 (m, 2 H), 3.91 (m, 2 H), 3.74 (m, 3 H), 2.08 (m, 1 H), 1.74 (m, 1 H), 1.60 (m, 3 H), 1.12 (m, 6 H). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 151.72 (C), 144.45 (C), 142.31 and 142.26 (C), 129.73 and 129.68 (CH), 129.23 and 129.20 (CH), 128.67 and 128.59 (CH), 128.56 and 128.54 (CH), 110.03 and 109.97 (C), 89.84 and 89.76 (CH), 88.35 and 88.76 (CH), 86.07 and 86.04 (CH), 74.59 (CH), 71.93 and 71.86 (CH), 64.46 and 63.96 (CH2), 63.08 and 63.02 (CH2), 45.74 (CH), 30.77 and 30.67 (CH2), 30.49 and 30.44 (CH2), 27.68 (CH2), 27.19 (CH2), 27.14 (CH2). HRMS (ESI ⁺ ) for [MH] ⁺ C23H32N3O7 calculated: 462.22403, observed: 462.23198. Example 76 [0155] 5-[1-phenyl-1-(cyclohexyl)methoxymethyl]cytidine (VAL-1-89 – RIID1263 was prepared by the following procedure and with the following results: Treatment of 5- [1-phenyl-1-(cyclohexyl)methoxymethyl]-2′,3′,5′-tris-O -(tert-butyldimethylsilyl)cytosine (17 mg, 0.311 mmol) afforded 2 mg of product (23%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.91 and 7.86 (2 s, 1 H), 7.31 (m, 5 H), 5.83 and 5.80 (2 d, 1 H, J = 2.7 Hz), 4.15 (m, 3 H), 4.00 (m, 3 H), 3.85 (m, 1 H), 3.71 (m, 1 H), 2.10 (m, 1 H), 1.71 (m, 1 H), 1.62 (m, 2 H), 1.20 (m, 5 H), 0.90 (m, 2 H). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 166.64 (C), 158.26 and 158.16 (C), 142.44 and 142.33 (CH), 141.96 and 141.67 (C), 129.47 and 129.39 (CH), 128.89 and 128.78 (CH), 128.82 and 128.73 (CH), 105.15 and 104.98 (C), 92.35 and 92.21 (CH), 87.80 and 87.08 (CH), 85.87 and 85.74 (CH), 76.30 and 76.20 (CH), 70.78 and 70.46 (CH), 66.10 and 65.58 (CH2), 61.97 and 61.80 (CH2), 45.54 and 45.42 (CH), 30.75 (CH2), 30.45 and 30.42 (CH2), 27.60 (CH2), 27.10 (CH2), 27.04 (CH2). HRMS (ESI ⁺ ) for [MH] ⁺ C23H32N3O7 calculated: 446.22911, observed: 446.23589. Example 77 [0156] 5-[1-(phenyl)ethoxymethyl]-4-N-(hydroxy)cytidine (VAL-1-156 – RIID1359 was prepared by the following procedure and with the following results: Treatment of 5- [1-(phenyl)ethoxymethyl]-4-N-hydroxy-2′,3′,5′-tris-O-( tert-butyldimethylsilyl)cytosine (14 mg, 0.018 mmol) afforded 6 mg of product (85%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.34 (m, 4 H), 7.26 (m, 1 H), 7.17 and 7.14 (2 s, 1 H); 5.88 and 5.87 (2 d, 1 H, J = 5.5 and 5.2 Hz), 4.55 (q, 1 H, J = 6.5 Hz), 4.10 (m, 4 H), 3.95 (m, 1 H), 3.77 (m, 1 H), 3.71 (m, 1 H), 1.43 and 1.42 (2 d, 1 H, J = 6.5 Hz). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 151.72 (C), 144.86 and 144.83 (C), 144.52 (C), 129.91 and 129.82 (CH), 129.53 and 129.51 (CH), 128.59 and 128.57 (CH), 127.33 (CH), 109.81 and 109.79 (C), 89.86 and 89.78 (CH), 86.07 (CH), 79.33 and 79.23 (CH), 74.69 and 74.65 (CH), 71.85 and 71.82 (CH), 64.29 and 64.21 (CH2), 62.88 (CH2), 24.42 and 24.36 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C18H24N3O7 calculated: 394.16143, observed: 394.16700. Example 78 [0157] 5-[1-(phenyl)ethoxymethyl]cytidine (VAL-2-4 – RIID1360 was prepared by the following procedure and with the following results: Treatment of 5-[1- (phenyl)ethoxymethyl]-2′,3′,5′-tris-O-(tert-butyldimet hylsilyl)cytosine (24 mg, 0.033 mmol) afforded 6 mg of product (48%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.98 and 7.95 (2 s, 1 H); 7.34 (m, 4 H), 7.28 (m, 1 H), 5.83 and 5.80 (2 d, 1 H, J = 2.6 and 3.2 Hz), 4.51 (m, 1 H), 4.20 (m, 2 H), 4.11 (m, 2 H), 4.01 (m, 1 H), 3.87 (m, 1 H), 3.75 (m, 1 H), 1.44 and 1.43 (2 d, 1 H, J = 6.4 Hz). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 166.61 (C), 158.26 (C), 144.45 and 144.18 (C), 142.37 and 142.32 (CH), 129.73 and 129.67 (CH), 128.89 and 128.81 (CH), 127.48 and 127.39 (CH), 105.11 and 104.98 (C), 92.35 and 92.27 (CH), 85.80 and 85.70 (CH), 78.85 and 78.31 (CH), 76.28 and 76.23 (CH), 70.65 and 70.39 (CH), 65.93 and 65.56 (CH2), 61.88 and 61.70 (CH2), 24.18 and 24.05 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C18H24N3O6 calculated: 378.16651, observed: 378.17191. Example 79 [0158] 5-[1-(phenyl)propoxymethyl]-4-N-(hydroxy)cytidine (VAL-2-16 – RIID1377 was prepared by the following procedure and with the following results: Treatment of 5- [1-(phenyl)propoxymethyl]-4-N-hydroxy-2′,3′,5′-tris-O- (tert-butyldimethylsilyl)cytosine (49 mg, 0.065 mmol) afforded 21 mg of product (80%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.30 (m, 4 H), 7.24 (m, 1 H), 7.15 and 7.12 (2 s, 1 H); 5.88 (2 d, 1 H, J = 5.5 Hz), 4.27 (t, 1 H, J = 6.6 Hz), 4.07 (m, 5 H), 3.77 (m, 1 H), 3.70 (m, 1 H), 1.83 (m, 1 H), 1.67 (m, 1 H), 0.87 (m, 3 H). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 151.70 (C), 144.49 (C), 143.49 and 143.41 (C), 129.83 (CH), 129.39 and 129.37 (CH), 128.61 and 128.58 (CH), 127.94 and 127.91 (CH), 109.89 and 109.85 (C), 89.85 and 89.78 (CH), 86.02 (CH), 84.99 and 84.86 (CH), 74.64 and 74.61 (CH), 71.84 and 71.80 (CH), 64.38 and 64.32 (CH2), 62.91 and 62.86 (CH2), 32.06 and 31.95 (CH2), 10.59 and 10.55 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C19H26N3O7 calculated: 408.17928, observed: 408.18535. Example 80 [0159] 5-[(1-phenyl)propoxymethyl]cytidine (VAL-2-17 – RIID1378 was prepared by the following procedure and with the following results: Treatment of 5-[(1- phenyl)propoxymethyl]-2′,3′,5′-tris-O-(tert-butyldimet hylsilyl)cytosine (28 mg, 0.038 mmol) afforded 11 mg of product (74%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.95 and 7.91 (2 s, 1 H); 7.31 (m, 5 H), 5.83 and 5.80 (2 d, 1 H, J = 2.8 and 3.2 Hz), 4.18 (m, 6 H), 3.85 (m, 1 H), 3.72 (m, 1 H), 1.86 (m 1 H), 1.68 (m, 1 H), 0.86 (m, 3 H). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 166.62 (C), 154.19 (C), 143.10 and 142.81 (C), 142.40 and 142.31 (CH), 129.65 and 129.58 (CH), 128.93 and 128.84 (CH), 128.09 and 128.00 (CH), 105.18 and 104.99 (C), 92.32 and 92.21 (CH), 85.83 and 85.70 (CH), 84.58 and 83.93 (CH), 76.29 and 76.21 (CH), 70.70 and 70.41 (CH), 66.03 and 65.57 (CH2), 61.91 and 61.72 (CH2), 31.88 and 31.75 (CH2), 10.58 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C19H26N3O6 calculated: 392.18216, observed: 392.18503. Example 81 [0160] 5-[(1-phenyl-2-methyl)propoxymethyl]-4-N-(hydroxy)cytidine (VAL-2-44 – RIID1388 was prepared by the following procedure and with the following results: Treatment of 5-[(1-phenyl-2-methyl)propoxymethyl]-4-N-hydroxy-2′,3′,5 ′-tris-O-(tert- butyldimethylsilyl)cytosine (20 mg, 0.026 mmol) afforded 9 mg of product (82%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.28 (m, 5 H), 7.13 and 7.09 (2 s, 1 H); 5.88 and 5.87 (2 d, 1 H, J = 5.2 and 5.5 Hz), 4.13 (m, 2 H), 4.04 (AB d, 1 H, J = 12.9 Hz), 3.95 (m, 3 H), 3.78 (m, 1 H), 3.70 (m, 1 H), 1.93 (m, 1 H), 1.02 (d, 3 H, J = 6.6 Hz), 0.73 (d, 3 H, J = 6.8 Hz). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 151.72 (C), 144.46 (C), 142.37 and 142.30 (C), 129.73 (CH), 129.62 (CH), 129.18 (CH), 128.65 and 128.56 (CH), 110.05 and 109.98 (C), 89.83 and 89.78 (CH), 89.08 and 88.83 (CH), 86.03 (CH), 74.58 (CH), 71.89 and 71.85 (CH), 64.53 (CH2), 62.99 and 62.94 (CH2), 36.03 and 35.98 (CH), 19.57 and 19.55 (CH3), 19.41 and 19.36 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C20H28N3O7 calculated: 422.17267, observed: 422.16975. Example 82 [0161] 5-[(1-phenyl-2-methyl)propoxymethyl]cytidine (VAL-2-45 – RIID1389 was prepared by the following procedure and with the following results: Treatment of 5-[(1- phenyl-2-methyl)propoxymethyl]-2′,3′,5′-tris-O-(tert-b utyldimethylsilyl)cytosine (17 mg, 0.023 mmol) afforded 3 mg of product (32%). ¹ H NMR (400 MHz, Methanol-d4) for 1:1 mixture of diastereomers δ 7.92 and 7.86 (2 s, 1 H); 7.30 (m, 5 H), 5.83 and 5.80 (2 d, 1 H, J = 3.1 and 3.2 Hz), 4.20 (m, 1 H), 4.06 (m, 3 H), 3.95 (dd, 1 H, J = 7.7, 4.8 Hz), 3.84 (m, 2 H), 3.71 (m, 1 H), 1.92 (m 1 H), 1.02 (2 d, 3 H, J = 6.6 Hz), 0.70 (2 d, 3 H, J = 6.8 Hz). ¹³ C NMR (100 MHz, CD3OD) for 1:1 mixture of diastereomers δ 165.76 (C), 154.44 (C), 142.43 and 142.30 (CH), 141.76 (C), 129.46 and 129.38 (CH), 128.90 and 128.79 (CH), 128.69 (CH), 104.99 (C), 92.33 and 92.20 (CH), 88.74 and 88.05 (CH), 85.86 and 85.71 (CH), 74.67 and 74.07 (CH), 70.77 and 70.44 (CH), 66.20 and 65.68 (CH2), 61.96 and 61.76 (CH2), 35.91 and 35.82 (CH2), 19.57 and 19.53 (CH3) , 19.11 and 19.08 (CH3). HRMS (ESI ⁺ ) for [MH] ⁺ C20H28N3O6 calculated: 406.17685, observed: 406.17468. Example 83 [0162] 5-[(benzyloxy)methyl]-4-N-(hydroxy)cytidine (VAL-1-131 - RIID1290 was prepared by the following procedure and with the following results: Treatment of 5- [(benzyloxy)methyl]-4-N-hydroxy-2′,3′,5′-tris-O-(tert- butyldimethylsilyl)cytosine (17 mg, 0.023 mmol) afforded 5 mg of product (52%). ¹ H NMR (400 MHz, Methanol-d4) δ 7.31 (m, 5 H), 7.27 (m, 1 H), 7.23 (s, 1 H), 5.87 (d, 1 H, J = 5.4 Hz), 4.56 (s, 2 H), 4.22 (AB dd, 1 H, J = 12.5, 1.0 Hz), 4.19 (AB d, 1 H, J = 12.5, 0.9 Hz), 4.16 (m, 1 H), 4.11 (dd, 1 H, J = 5.4, 4.0 Hz), 3.95 (q, 1 H, J = 3.5 Hz), 3.78 (AB dd, 1 H, J = 12.1, 3.0 Hz), 3.69 (AB dd, 1 H, J = 12.1, 3.6 Hz). ¹³ C NMR (100 MHz, Methanol-d4) δ 151.71 (C), 144.66 (C), 139.54 (C), 130.60 (CH), 129.39 (CH), 128.94 (CH), 128.71 (CH), 109.39 (C), 89.83 (CH), 86.08 (CH), 74.68 (CH), 73.51 (CH2), 71.76 (CH), 65.93 (CH2), 62.83 (CH2). HRMS (ESI ⁺ ) for [MH] ⁺ C17H22N3O7 calculated: 380.14578, observed: 380.15342. Example 84 [0163] 5-[(benzyloxy)methyl]cytidine (VAL-1-132 – RIID1291 was prepared by the following procedure and with the following results: Treatment of 5-[(benzyloxy)methyl]- 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)cytosine (7 mg, 0.010 mmol) afforded 2 mg of product (58%). ¹ H NMR (400 MHz, Methanol-d4) δ 8.14 (s, 1 H), 7.34 (m, 5 H), 5.84 (d, 1 H, J = 2.9 Hz), 4.52 (s, 2 H), 4.36 (AB d, 1 H, J = 11.9 Hz), 4.34 (AB d, 1 H, J = 11.9 Hz), 4.22 (dd, 1 H, J = 5.8, 1.8 Hz), 4.12 (m, 1 H), 4.03 (m, 1 H), 3.91 (AB dd, 1 H, J = 12.4, 2.6 Hz), 3.76 (AB dd, 1 H, J = 12.4, 2.9 Hz). ¹³ C NMR (100 MHz, Methanol-d4) δ 166.31 (C), 155.22 (C), 142.38 (CH), 137.00 (CH), 129.86 (CH), 129.48 (CH), 128.44 (CH), 106.87 (C), 89.31 (CH), 83.04 (CH), 77.32 (CH), 76.26 (CH2), 70.41 (CH), 69.11 (CH2), 67.38 (CH2). HRMS (ESI ⁺ ) for [MH] ⁺ C17H22N3O6 calculated: 364.15086, observed: 364.15765. Example 85 [0164] 5-[{2-chloro(benzyloxy)}methyl]-4-N-(hydroxy)cytidine (VAL-2-30 - RIID1382 was prepared by the following procedure and with the following results: Treatment of 5-[{2-chloro(benzyloxy)}methyl]-4-N-hydroxy-2′,3′,5′-t ris-O-(tert- butyldimethylsilyl)cytosine (6 mg, 0.008 mmol) afforded 3 mg of product (95%). ¹ H NMR (400 MHz, Methanol-d4) δ 7.56 (m, 1 H), 7.37 (m, 1 H), 7.28 (m, 3 H), 5.88 (d, 1 H, J = 5.5 Hz), 4.67 (s, 2 H), 4.29 (AB d, 1 H, J = 12.0 Hz), 4.25 (AB d, 1 H, J = 12.0 Hz), 4.16 (m, 1 H), 4.12 (m, 1 H), 3.95 (m, 1 H), 3.78 (AB dd, 1 H, J = 12.1, 3.0 Hz), 3.69 (AB dd, 1 H, J = 12.1, 3.4 Hz). ¹³ C NMR (100 MHz, Methanol-d4) δ 151.86 (C), 144.63 (C), 137.16 (C), 133.99 (C), 130.73 (CH), 130.58 (CH), 130.25 (CH), 130.02 (CH), 128.05 (CH), 109.30 (C), 89.83 (CH), 86.11 (CH), 74.69 (CH), 71.78 (CH), 70.54 (CH2), 66.43 (CH2), 62.85 (CH2). HRMS (ESI ⁺ ) for [MH] ⁺ C17H21 ³⁵ ClN3O7 calculated: 414.10680, observed: 414.10685. Example 86 [0165] 5-[{2-chloro(benzyloxy)}methyl]cytidine (VAL-2-31 – RIID1383 was prepared by the following procedure and with the following results: Treatment of 5-[{2- chloro(benzyloxy)}methyl]-2′,3′,5′-tris-O-(tert-butyld imethylsilyl)cytosine (6 mg, 0.008 mmol) afforded 2 mg of product (58%). ¹ H NMR (400 MHz, Methanol-d4) δ 8.20 (s, 1 H), 7.50 (m, 1 H), 7.38 (m, 1 H), 7.30 (m, 2 H), 5.85 (d, 1 H, J = 3.0 Hz), 4.63 (s, 2 H), 4.45 (AB d, 1 H, J = 12.0 Hz), 4.41 (AB d, 1 H, J = 12.0 Hz), 4.14 (m, 2 H), 4.03 (m, 1 H), 3.92 (AB dd, 1 H, J = 12.3, 2.5 Hz), 3.77 (AB dd, 1 H, J = 12.3, 3.0 Hz). ¹³ C NMR (100 MHz, Methanol-d4) δ 166.00 (C), 151.62 (C), 142.87 (CH), 136.76 (C), 134.30 (C), 132.82 (CH), 131.02 (CH), 130.37 (CH), 128.16 (CH), 103.18 (C), 92.26 (CH), 85.82 (CH), 76.31 (CH), 70.46 (CH), 70.04 (CH2), 63.05 (CH2), 61.74 (CH2). HRMS (ESI ⁺ ) for [MH] ⁺ C17H21ClN3O6 calculated: 398.11419, observed: 398.12041. Example 87 [0166] 5-[(hydroxy)methyl]-4-N-(hydroxy)cytidine (VAL-1-139 - RIID1294 was prepared by the following procedure and with the following results: Treatment of 5-[(tert- butyldimethylsilyloxy)methyl]-4-N-hydroxy-2′,3′,5′-tri s-O-(tert-butyldimethylsilyl)cytosine (108 mg, 0.145 mmol) followed by purification by column chromatography (SiO2, Dichloromethane/Methanol eluting from 20:1 to 10:1 afforded 10 mg of product (24%). ¹ H NMR (400 MHz, Methanol-d4) δ 7.18 (s, 1 H), 5.91 (d, 1 H, J = 5.7 Hz), 4.56 (s, 2 H), 4.19 (t, 1 H, J = 5.6 Hz), 4.14 (m, 1 H), 3.97 (q, 1 H, J = 3.5 Hz), 3.81 (AB dd, 1 H, J = 12.1, 3.0 Hz), 3.72 (AB dd, 1 H, J = 12.1, 3.6 Hz). ¹³ C NMR (100 MHz, Methanol-d4) δ 151.80 (C), 144.58 (C), 128.95 (CH), 112.32 (C), 89.74 (CH), 86.06 (CH), 74.53 (CH), 71.78 (CH), 62.89 (CH2), 58.26 (CH2). HRMS (ESI ⁺ ) for [MH] ⁺ C10H16N3O7 calculated: 290.09882, observed: 290.10192. Example 88 [0167] 5-[methoxymethyl]uracil (VAL-2-46 - RIID1385) was prepared exactly as described previously.i ^{ii 1} H NMR (400 MHz, Methanol-d4) δ 7.42 (s, 1 H), 4.14 (s, 2 H), 3.36 (s, 3 H). ¹³ C NMR (100 MHz, CD3OD) δ 166.14 (C), 153.43 (C), 141.96 (CH), 111.22 (C), 67.67 (CH2), 58.40 (CH3). Example 89 [0168] 5-[(hydroxy)methyl]cytidine (RIID1293) was available from Toronto Research (catalog #H947090). REFERENCES 1. Burke MP, Borland KM, Litosh, VA. Base-Modified Nucleosides as Chemotherapeutic Agents: Past and Future. Curr. Topics Med. Chem. 2016;16(11):1231-1241. doi: 10.2174/1568026615666150915111933. 2. Lolkema MP, Arkenau H-T, Harrington K, Roxburgh P, Morrison R, Roulstone V, Twigger K, Coffey M, Mettinger K, Gill G, Evans TRJ, de Bono JS. A Phase I Study of the Combination of Intravenous Reovirus Type 3 Dearing and Gemcitabine in Patients with Advanced Cancer. Clin. Cancer Res.2011;17(3):581-588. doi: 10.1158/1078-0432.ccr-10-2159. 3. Cannas G, Pautas C, Raffoux E, Quesnel B, de Botton S, de Revel T, Reman O, Gardin C, Elhamri M, Boissel N, Fenaux P, Michallet M, Castaigne S, Dombret H, Thomas X. Infectious complications in adult acute myeloid leukemia: analysis of the Acute Leukemia French Association-9802 prospective multicenter clinical trial. Leuk. Lymphoma 2012;53(6):1068-1076. doi: 10.3109/10428194.2011.636812. PubMed PMID: 22145959. 4. Painter GR, Bowen RA, Bluemling GR, DeBergh J, Edpuganti V, Gruddanti PR, Guthrie DB, Hager MK, Damien L, Lockwood MA, Mitchell DG, Natchus, MG, Sticher, ZM, Kolykhanov, AA. The prophylactic and therapeutic activity of a broadly active ribonucleoside analog in a murine model of intranasal venezuelan equine encephalitis virus infection. Antiviral Res 2019;171:104597. doi: 10.1016/j.antiviral.2019.104597. 5. Reynard O, Nguyen X-N, Alazard-Dany N, Barateau V, Cimarelli A, Volchkov VE. Identification of a new ribonucleoside inhibitor of Ebola virus replication. Viruses 2015;7(12):6233-6240. doi: 10.3390/v7122934. 6. Costantini VP, Whitaker T, Barclay L, Lee D, McBrayer TR, Schinazi RF, Vinjé J. Antiviral activity of nucleoside analogues against norovirus. Antiviral Ther. 2012;17(6):981-991. doi: 10.3851/IMP2229. 7. Sheahan TP, Sims AC, Zhou S, Graham RL, Pruijssers AJ, Agostini ML, Leist SR, Schäfer A, Dinnon III KH, Stevens LJ, Chappell JD, Lu X, Hughes TM, George AS, Hill CS, Montgomery SA, Brown AJ, Bluemling GR, Natchus MG, Saindane M, Kolykhalov AA, Painter G, Harcourt J, Tamin A, Thornburg NJ, Swanstrom R, Denison MR, Baric RS. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Sci. Transl. Med.2020;12(541):eabb5883. doi: 10.1002/1098-1128(200011)20:6<417::AID- MED1>3.0.CO;2-Z. 8. Jena NR. Role of different tautomers in the base-pairing abilities of some of the vital antiviral drugs used against COVID-19. Phys. Chem. Chem. Phys. 2020;22:28115-28122. doi: 10.1039/D0CP05297C 9. Suzuki T, Moriyama K, Otsuka C, Loakes D, Negishi, K. Template properties of mutagenic cytosine analogues in reverse transcription. Nucleic Acids Res. 2006;34(22): 6438–6449. doi: 10.1093/nar/gkl761. 10. De Serres FJ, Brockman HE. Comparison of the spectra of genetic damage in N4-hydroxycytidine-induced ad-3 mutations between nucleotide excision repair-proficient and -deficient heterokaryons of Neurospora crassa. Mutation Res. 1993;285(2):145-163. doi: 10.1016/0027-5107(93)90102-L. 11. Negishi K, Harada C, Ohara Y, Oohara K, Nitta N, Hayatsu H. N4- Aminocytidine, a nucleoside analog that has an exceptionally high mutagenic activity. Nucleic Acids Res.1983;11(15): 5223–5233. 12. Litosh VA, Wu W, Stupi BP, Wang J, Morris SE, Hersh MN, Metzker ML. Improved nucleotide selectivity and termination of 3′-OH unblocked reversible terminators by molecular tuning of 2-nitrobenzyl alkylated HOMedU triphosphates. Nucleic Acids Research.2011;39(6):e39. doi: 10.1126/scitranslmed.abb5883. 13. Wu W, Stupi BP, Litosh VA, Mansouri D, Morris SE, Metzker S, Metzker ML, Termination of DNA Synthesis by N6-alkylated, not 3′-alkylated, Photocleavable 2′- Deoxyadenosine Triphosphates. Nucleic Acids Res.2007;35(19):6339-6349. doi: 10.1093/nar/gkm689. 14. Stupi BP, Li H, Wang J, Wu W, Morris SE, Litosh VA, Muniz J, Hersh MN, Metzker ML. Stereochemistry of Benzylic Carbon Substitution Coupled with Ring Modification of 2-Nitrobenzyl Groups as Key Determinants for Fast-Cleaving Reversible Terminators. Angewandte Chemie International Edition.2012;51(7):1724-1727. doi: 10.1002/anie.201106516. 15. Borland KM, AbdulSalam SF, Solivio MJ, Burke MP, Wolfkiel PR, Lawson SM, Stockman CA, Andersen JM, Smith S, Tolstolutskaya JN, Gurjar PN, Bercz AP, Merino EJ, Litosh VA. Base-modified thymidines capable of terminating DNA synthesis are novel drug candidates with activity in cancer cells. Bioorganic & Medicinal Chemistry.2015;23(8):1869-1881. doi: 10.1016/j.bmc.2015.01.057 16. Bercz AP, McClure WA, English M, Keebaugh MW, Litosh VA, Stereochemistry of the α-carbon in benzylic modifying moiety attached at the C-5 end of thymidine affects the potency of a newly identified anti-cancer lead nucleoside. Tetrahedron 2020;76(52):131705. doi: 10.1016/j.tet.2020.131705 17. Borland KM, Wolfkiel PR, Burke MP, Lawson SM, Stockman CA, Bercz AP, Tolstolutskaya JN, Litosh, VA. Base-modified thymidine and thymine analogs with low cytotoxicity effectively obstruct DNA replication in papovaviridae. Bio Chem. Comp. 2016;4:3. doi: 10.7243/2052-9341-4-3 18. Siegel R, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA: A Cancer J. Clin.2021;71(1):7-33. doi: 10.3322/caac.21654. 19. Zhang J, Visser F, King KM, Baldwin SA, Young JD, Cass CE. The role of nucleoside transporters in cancer chemotherapy with nucleoside drugs. Cancer and Metastasis Reviews.2007;26(1):85-110. doi: 10.1007/s10555-007-9044-4. 20. Eriksson S, Munch-Petersen B, Johansson K, Ecklund H. Structure and function of cellular deoxyribonucleoside kinases. Cellular and Molecular Life Sciences. 2002;59(8):1327-1346. doi: 10.1007/s00018-002-8511-x. 21. Chen LS, Plunkett W, Gandhi V. Polyadenylation inhibition by the triphosphates of deoxyadenosine analogues. Leukemia Research.2008;32(10):1573- 1581. doi: 10.1016/j.leukres.2008.03.010. 22. Kuchta RD, Ilsley D, Kravig KD, Schubert S, Harris B. Inhibition of DNA primase and polymerase .alpha. by arabinofuranosylnucleoside triphosphates and related compounds. Biochemistry.1992;31(19):4720-4728. doi: 10.1021/bi00134a027. 23. Parker WB, Shaddix SC, Chang C-H, White EL, Rose LM, Brockman RW, Shortnacy AT, Montgomery JA, Secrist JA 3rd, Bennett LL Jr. Effects of 2-Chloro-9-(2- deoxy-2-fluoro-β-d-arabinofuranosyl)adenine on K562 Cellular Metabolism and the Inhibition of Human Ribonucleotide Reductase and DNA Polymerases by Its 5′- Triphosphate. Cancer Res.1991;51(9):2386-2394. PubMed PMID: 1707752 24. Peters GJ, van der Wilt CL, van Groeningen CJ, Smid K, Meijer S, Pinedo HM. Thymidylate synthase inhibition after administration of fluorouracil with or without leucovorin in colon cancer patients: implications for treatment with fluorouracil. J. Clin. Oncol.1994;12(10):2035-2042. doi: 10.1200/JCO.1994.12.10.2035. PubMed PMID: 7931471. 25. Hill DL, Bennett LL. Purification and properties of 5- phosphoribosylpyrophosphate amidotransferase from adenocarcinoma 755 cells. Biochemistry.1969;8(1):122-130. doi: 10.1021/bi00829a017. 26. Fairchild CR, Maybaum J, Kennedy KA. Concurrent unilateral chromatid damage and DNA strand breakage in response to 6-thioguanine treatment. Biochem. Pharmacol.1986;35(20):3533-3541.doi: 10.1016/0006-2952(86)90623-4 27. Swann PF, Waters TR, Moulton DC, Xu Y-Z, Zheng Q, Edwards M, Mace R. Role of Postreplicative DNA Mismatch Repair in the Cytotoxic Action of Thioguanine. Science.1996;273(5278):1109-1111. doi: 10.1126/science.273.5278.1109. 28. Peterli S, Hubmann D, Séquin U, Mett H, Traxler P. Nitrostyrene Derivatives of Adenosine 5′-Glutarates Modified with an Alkyl Spacer and their inhibitory activity on epidermal growth factor receptor protein tyrosine kinase. Helv. Chim. Acta. 1994;77(1):59-69. doi: 10.1002/hlca.19940770109. 29. Tak-Tak L, Barbault F, Maurel F, Busca P, Le Merrer Y. Synthesis of purin-2-yl and purin-6-yl-aminoglucitols as C-nucleosidic ATP mimics and biological evaluation as FGFR3 inhibitors. Eur. J. Med. Chem.2011;46(4):1254-1262. doi: 10.1016/j.ejmech.2011.01.048. 30. Genini D, Adachi S, Chao Q, Rose DW, Carrera CJ, Cottam HB, Carson DA, Leoni LM. Deoxyadenosine analogs induce programmed cell death in chronic lymphocytic leukemia cells by damaging the DNA and by directly affecting the mitochondria. Blood.2000;96(10):3537-3543. PubMed PMID: 11071652. 31. Lee KS, Ro J, Lee ES, Kang HS, Kim SW, Nam B-H, Kwon Y, Kim E-A, Shin KH. Primary systemic therapy with intermittent weekly paclitaxel plus gemcitabine in patients with stage II and III breast cancer: a phase II trial. Invest. New Drugs. 2010;28(1):83-90. doi: 10.1007/s10637-009-9229-5. PubMed PMID: 19229476. 32. Pippen J, Elias AD, Neubauer M, Stokoe C, Vaughn LG, Wang Y, Orlando M, Shonukan O, Muscato J, O'Shaughnessy JA, Gralow J. A phase II trial of pemetrexed and gemcitabine in patients with metastatic breast cancer who have received prior taxane therapy. Clin. Breast Cancer.2010;10(2):148-153. doi: 10.3816/CBC.2010.n.020. PubMed PMID: 20299319. 33 Ando M, Watanabe T, Sasaki Y, Ying DF, Omuro Y, Katsumata N, Narabayashi M, Tokue Y, Fujii H, Igarashi T, Wakita H, Ohtsu T, Itoh K, Adachi I, Taguchi T. A phase I trial of docetaxel and 5-day continuous infusion of 5-fluorouracil in patients with advanced or recurrent breast cancer. Br. J. Cancer.1998;77(11):1937- 1943. doi: 10.1038/bjc.1998.321. 34. Dahan L, Ciccolini J, Evrard A, Mbatchi L, Tibbitts J, Ries P, Norguet E, Mercier C, Iliadis A, Ouafik L’H, Lacarelle B, Seitz J-F. Sudden Death Related to Toxicity in a Patient on Capecitabine and Irinotecan Plus Bevacizumab Intake: Pharmacogenetic Implications. J. Clin. Oncol.2012;30(4):e41-e44. doi: 10.1200/jco.2011.37.9289. 35. Mounier-Boutoille H, Boisdron-Celle M, Cauchin E, Galmiche J-P, Morel A, Gamelin E, Matysiak-Budnik T. Lethal outcome of 5-fluorouracil infusion in a patient with a total DPD deficiency and a double DPYD and UTG1A1 gene mutation. Br. J. Clin. Pharmacol.2010;70(2):280-283. doi: 10.1111/j.1365-2125.2010.03686.x. PubMed PMID: 20653683. 36. Willemsen AECAB, van Herpen CML, Wesseling P, Bult P, van Laarhoven HWM. Fatal thrombotic microangiopathy after a single dose of gemcitabine as fourth- line palliative treatment for metastasized ductal breast carcinoma. Acta Oncolog. 2011;50(3):462-465. doi: 10.3109/0284186X.2010.491088. PubMed PMID: 20799915. 37. Krishna IV, Vanaja GR, Kumar NSK, Suman G. Cytotoxic studies of anti- neoplastic drugs on human lymphocytes – In vitro studies. Cancer Biomarkers. 2009;5(6):261-272. doi: 10.3233/CBM-2009-0111. PubMed PMID: 47100634. 38. Cordier P-Y, Nau A, Ciccolini J, Oliver M, Mercier C, Lacarelle B,Peytel, E. 5-FU-induced neurotoxicity in cancer patients with profound DPD deficiency syndrome: a report of two cases. Cancer Chemother. Pharmacol.2011;68(3):823-826. doi: 10.1007/s00280-011-1666-0. PubMed PMID: 21553285. 39. Sun J, Damaraju VL, Cass CE, Sawyer MB. Inhibition of nucleoside transporters by tyrosine kinase inhibitors and its effects on chemotherapy efficacy. Cancer Cell Microenvironment.2014;1(6):e389. doi: 10.14800/ccm.389. 40. Ramalingam S, Belani C. Systemic Chemotherapy for Advanced Non- Small Cell Lung Cancer: Recent Advances and Future Directions. Oncologist. 2008;13(S1):5-13. doi: 10.1634/theoncologist.13-S1-5. PubMed PMID: 18263769. 41. Hajjaji N, Bougnoux P. Selective sensitization of tumors to chemotherapy by marine-derived lipids: A review. Cancer Treat. Rev.2013;39(5):473-488. doi: 10.1016/j.ctrv.2012.07.001. PubMed PMID: 22850619. 42. Damaraju VL, Scriver T, Mowles D, Kuzma M, Ryan AJ, Cass CE, Sawyer MB. Erlotinib, Gefitinib, and Vandetanib Inhibit Human Nucleoside Transporters and Protect Cancer Cells from Gemcitabine Cytotoxicity. Clin. Cancer Res.2014;20(1):176- 186. doi: 10.1158/1078-0432.ccr-13-2293. PubMed PMID: 24170548. 43 Meeran MFN, Charu S, Goyal SN, Kumar S, Ojha S. CB2 receptor- selective agonists as candidates for targeting infection, inflammation, and immunity in SARS-CoV-2 infections. Drug Dev. Res.2021;82(1):7-11. doi: 10.1002/ddr.21752. 44. Yamazaki S, Suzuki T, Sayama M, Nakada T, Igari H, Ishii I. Suspected cholestatic liver injury induced by favipiravir in a patient with COVID-19. J. Infect. Chemother.2021;27(2):390-392. doi: 10.1016/j.jiac.2020.12.021. 45. Calcagno A, Moltó J, Borghetti A, Gervasoni C, Milesi M, Valle M, Avataneo V, Alcantarini C, Pla-Junca F, Trunfio M, D'Avolio A, Di Giambenedetto S, Cattaneo D, Di Perri G, Bonora S. Older Age is Associated with Higher Dolutegravir Exposure in Plasma and Cerebrospinal Fluid of People Living with HIV. Clin Pharmacokinet.2021;60(1):103-109. doi: 10.1007/s40262-020-00916-9. PubMed PMID: 32737820. 46. Lim TS, Lee JS, Kim BK, Lee HW, Jeon MY, Kim SU, Park JY, Kim DY, Han KH, Ahn SH. An observational study on long‐term renal outcome in patients with chronic hepatitis B treated with tenofovir disoproxil fumarate. J. Viral Hep.2020; 27(3):316-322. doi: 10.1111/jvh.13222. 47. Abo-zeid Y, Urbanowicz RA, Thomson BJ, Irving WL, Tarr AW, Garnett MC. Enhanced nanoparticle uptake into virus infected cells: Could nanoparticles be useful in antiviral therapy? Int. J. Pharm.2018; 547(1-2):572-581. doi: 10.1016/j.ijpharm.2018.06.027. 48. Yang L, Chen L, Zeng R, Li C, Qiao R, Hu L, Li Z. Synthesis, nanosizing and in vitro drug release of a novel anti-HIV polymeric prodrug: Chitosan-O-isopropyl-5′- O-d4T monophosphate conjugate. Bioorg. Med. Chem.2010; 18(1):117-123. doi: 10.1016/j.bmc.2009.11.013.