The present invention also relates to a process for preparing the compound of formula (I), as defined above, and an anti-cancer composition containing the compound of formula (I) as an active ingredient.

BACKGROUND ART It has been noted that taxaneterpine-based compounds inhibit the growth of various cancer cells and tumor cells to exhibit a very excellent anti-cancer effect of treating numerous cancers, leukemia and tumors. As typical example of such taxaneterpine-based compounds, paclitaxel (Taxol) represented by the following formula (II) can be mentioned: Paclitaxel represented by formula (II), as defined above, is the material extracted and separated from the cortex of Taxus brevifolia which is a yew tree grown on the shore of the Pacific. It has a good anti-cancer activity and therefore, has been used for treatment of ovarian cancer, breast cancer, lung cancer, etc. However, since paclitaxel can be provided only in a very limited amount from Taxus brevifolia which grows very slowly, the quantity of paclitaxel required in the clinical field cannot be satisfied. Furthermore, paclitaxel also has a disadvantage in that its use in the clinical field is extremely stricted, because it is very slightly soluble in water [0.0008mg/mQ; see, R. M. Straubinger, et al., Taxane Anticancer Agents, Basic Science and Current Status, ACS Symposium Series 583,1995, ppl 11-123] and therefore, has some problems related to the formulation and biological availability of pharmaceutical preparation. Due to such low water solubility, in order to dissolve paclitaxel in water it is necessary to use any special means or adjuvants and the dosage of paclitaxel to be administered to patients should also be restrictively adjusted. However, the adjuvants used for such purpose may also cause many side effects.

The study has been extensively conducted to improve the problems involved in paclitaxel as mentioned above. As a result, some French researchers have developed docetaxel (Taxotare; International Patent No. 94/ 12482) represented by the following formula (III), which is different from paclitaxel in view of the fact that acetyl group present in 10-position is removed and the substituent present in 13-position is changed: However, although docetaxel provides considerably improved water solubility and anti-cancer activity in comparison to paclitaxel, it could not completely solve the problem related to water solubility.

Recently, as a result of another study to increase the solubility of paclitaxel in water, the compound represented by the following formula (IV) in which a ketone group present in 9-position of taxaneterpine structure is reduced to a hydroxy group has been reported [see, T. P. Pulicani, et al., Tetrahedron Letters 1994,35,4999 and G. I. Georg, et al., Tetrahedron Letters 1995,36, 1783]: It has been noted that the taxaneterpine compound of formula (IV) in which the 9-ketone group is reduced to 9?-hydroxy group has an increased water solubility which is 10 times or more as high as docetaxel, and exhibits a substantially comparable in-vitro anti-cancer activity to paclitaxel.

As further study to increase the solubility of taxaneterpine compounds in water, the compound represented by the following formula (V) in which a hydroxy group is introduced into 14-position of taxaneterpine structure has been disclosed [see, International Patent No. 94/22856]. Specifically, it has been reported that when the hydroxy group is introduced into 14-position of taxaneterpine structure as shown in formula (V), the water solubility increases, the pharmacological activity is improved and thus, the toxicity and side effects can be diminished [see, Ojima, et al., J. Bioorg. Med. Chem. 1994,4,1571 and J. Kant, et al., J. Bioorg. Med. Chem. 1994,4,1565].

However, in spite of various attempts to increase the water solubility of taxaneterpine compounds having anti-cancer activity as mentioned above, the novel anti-cancer agent having a markedly increased water solubility and also having an excellent anti-cancer acitivity has not yet been developed. Moreover, the prior taxaneterpine anti-cancer agents such as paclitaxel of formula (II) and docetaxel of formula (III), which have been currently used for the clinical purpose, have a very low solubility in water and therefore, should be formulated into the injectable preparation using the mixture of 50% ethanol and 50% polyoxyethylcastor oil and then infused into the patient over many hours. However, such a mixed solvent used in formulating the injectbale preparation exhibits some effects harmful to human body and furthermore, paclitaxel and docetaxel themselves have serious side effects such as neutropenia, leukopenia, anemia, hypersensitivity, peripheral nervous disorders, myalgia, arthralgia, gastro-intestinal disorders (nausea and vomiting), etc. Therefore, it is still urgently required to develop a new agent which can significantly improve the anti-cancer activity and water solubility to solve numerous problems involved in the prior taxaneterpine-based anti-cancer agents and thus, can also remove the problems of side effects.

Thus, the present inventors have extensively and continuously conducted the study to develop the anti-cancer agent having a new structure which improves the problem of a low water solubility involved in the prior taxaneterpine-based anti-cancer agents and also provides an increased anti-cancer activity. As a result, we have identified that a 10-deacetyl-9-deketo-9ß, 14ß -dihydroxytaxane compound represented by formula (I), as defined above, in which hydroxy groups are introduced into 9, 8-position and 14 a-position of the taxaneterpine structure provides both a high water solubility and a superior anti-cancer activity, and therefore, completed the present invention.

DISCLOSURE OF THE INVENTION Accordingly, the first purpose of the present invention is to provide a novel taxaneterpine compound represented by formula (I), as defined above, which is useful as an anti-cancer agent.

Another purpose of the present invention is to provide a process for preparing the compound of formula (I) as defined above.

Still another purpose of the present invention is provide an anti-cancer composition which comprises the compound of formula (I) as an active ingredient, together with a pharmaceutically acceptable carrier.

BEST MODE FOR CARRYING OUT THE INVENTION The present invention relates to a novel taxaneterpine compound, i. e.

10-deacetyl-9-deketo-9ß, 14ß-dihydroxytaxane derivative, represented by the following formula (I), which is formed by introducing hydroxy groups into both 9, 8-position and 14, 8-position of the taxaneterpine structure and is useful as an anti-cancer agent: in which R'represents substituted or unsubstituted, straight or branched alkyl, alkenyl or alkynyl, substituted or unsubstituted aryl or heteroaryl, substituted or unsubstituted cycloalkyl, heterocycloalkyl, cycloalkenyl or heterocyclo- alkenyl; R2 represents substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl, or represents a radical of RO-, RS-or RR6N-, wherein R represents substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, hetero- cycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl and R6 represents hydrogen or has the same meaning as defined for R or R and R6 can together form a cyclic structure; R3 represents hydrogen, acyl, alkyl, alkenyl, alkynyl, substituted or unsubstituted cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, substituted or unsubstituted aryl, heteroaryl or a hydroxy protecting group; R4 represents hydrogen, acyl, alkyl, alkenyl, alkynyl, substituted or unsubstituted cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, substituted or unsubstituted aryl, heteroaryl or a hydroxy protecting group, or R3 and R4 can together form cyclic carbonate, cyclic thiocarbonate or acetonide structure; and R5 represents aryl.

Preferable compounds according to the present invention include the compound of formula (I) wherein R'represents alkyl, alkenyl, heterocycloalkyl, aryl or heteroaryl, R2 represents aryl, heteroaryl, cycloalkyl or a radical RO- wherein R represents alkyl, R3 and R4 independently of one another represent<BR> hydrogen or R3 and R4 can together form a cyclic structure, and R'represents phenyl.

More preferable compounds according to the present invention include the compound of formula (I) wherein R1 represents C,-C4 alkyl, C2-C6 alkenyl, heterocycloalkyl, phenyl or heteroaryl, R2 represents phenyl, heteroaryl, cycloalkyl or a radical RO-wherein R represents C1-C4 alkyl, R3 and R4 independently of one another represent hydrogen or R3 and R4 can together form cyclic carbonate or cyclic thiocarbonate structure and R 5 represents phenyl.

The most preferable compounds according to the present invention include the compound of formula (I) wherein Rl represents isopropyl, isobutyl, isobutenyl, tetrahydrofuranyl, phenyl, furyl, thiophenyl or pyridyl, R2 represents phenyl, furyl, cyclopropyl or t-butoxy, R3 and R4 independently of one another represent hydrogen or R3 and R4 can together form cyclic carbonate structure and R 5 represents phenyl.

It has been found that 10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxytaxane derivatives of formula (I), as defined above, according to the present invention have a markedly high solubility in water in comparison to the prior taxaneterpine anti-cancer agents such as paclitaxel and dositaxel and also have a superior anti-cancer activity against various types of cancer cells.

The present invention also relates to a process for preparing the novel taxaneterpine compound represented by formula (I), as defined above, which is useful as an anti-cancer agent.

According to the process of the present invention, the taxaneterpine compound of formula (I), i. e. 10-deacetyl-9-deketo-9ß, 14ß-dihydroxytaxane derivative can be prepared by reducing a ketone group present in the 9-position of a 10-deacetyl-14ß-hydroxytaxane derivative of formula (VI): in which each of R', R2, R3, R4 and R 5 has the same meaning as defined above.

The reducing agent which can be used for reduction of the 9-ketone group of the compound of formula (VI) according to the process of the present invention can include boron or aluminum-based reducing agents such as sodium borohydride (NaBH4), sodium cyanoborohydride (NaBH3CN), lithium borohydride (LiBI-L), tetrabutylammonium borohydride (n-Bu4NBH4), alan (AIH3), diisobutyl- alan (AIH [CH2CH (CH3) 2] 2), etc., or lanthanide-based reducing agents such as samarium iodide, etc.

As the reducing agent for the reduction according to the present invention, tetrabutylammonium borohydride (n-Bu4NBH4) or samarium iodide can be preferably used. Particularly, samarium iodide is most preferably used.

When samarium iodide is used as the reducing agent, it can be prepared from the reaction of samarium metal with iodine in tetrahydrofuran solvent and then immediately used in the reduction reaction. Alternatively, commercially available samarium iodide solution can also be used in the reduction. In this case, the reduction reaction is generally carried out in the presence of a solvent. The solvent which can be used for this purpose includes a mixed solvent of water and a water-miscible organic solvent. As the water-miscible organic solvent which can be used in the mixed solvent for the reaction according to the present invention, any of organic solvents which can dissolve all the compounds used in the reaction, do not participate in the reaction under the given reaction conditions, and can minimize the side reaction but maximize the reactivity, for example, alcools such as methanol, ethanol, etc., ethers such as tetrahydrofuran, 1,4-dioxane, etc., or amide solvents can be mentioned. In this reaction, it is preferable to use the mixed solvent of water and tetrahydrofuran in the ratio of 1: 5 to 1: 50 (v/v) as the solvent. The reduction is generally carried out at the temperature of-30°C to room temeprature and preferably at the temperature of-10°C to 10°C.

The 10-deacetyl-14ß-hydroxytaxane derivative of formula (VI) which is used as the starting material in the process according to the present invention has been known in International Patent No. 94/03215 or can be prepared by the process similar to the known method. For example, as illustrated in the following reaction scheme 1, the compound of formula (VI) wherein R3 and R4 independently of one another represent hydrogen can be prepared by protecting the functional groups of a 14/3-hydroxy-10-deacetylbaccatin (III) derivative of formula (VII) to obtain a derivative of formula (VIII), coupling the compound of formula (VIII) with a beta-lactam structure of isoserine derivative of formula (IX) as the side substituent group of taxaneterpine derivative to obtain a derivative of formula (X) and then removing the protecting groups from the compound of formula (X).

Reaction scheme 1 HO TrocO O O 0 0'0-0 HO HO'''protecting reaction HO, HO HO i H 0 0 0 Ho R,.-o/ (Vil) (vin) O R2 , TrocO R N TES (X) OTES OYES coupling reaction t O Õ ° eut0 R2 RUZ 0i'NH O 0-1-NH 0 HO OH deprotecting reaction Ouzo (VI) OH HO Hp-H : Rs 0 O In the above reaction scheme 1, each of R, R2 and R5 has the same meaning as defined above, Troc denotes 2,2,2-trichloroethoxycarbonyl, TES denotes triethylsilyl and Et denotes ethyl.

In addition, the compound of formula (VI) can be prepared by another method. Specifically, as illustrated in the following reaction scheme 2, the compound of formula (VI) wherein R3 and R4 together form a cyclic carbonate can be prepared by protecting the functional groups of the compound of formula (VII) and then cyclizing hydroxy groups present in 1 and 14-positions in the form of a carbonate to form a derivative of formula (XI), coupling the compound of formula (XI) with a beta-lactam structure of isoserine derivative of formula (IX) as the side substituent group of taxaneterpine derivative to obtain a derivative of formula (XII) and then removing the protecting groups from the compound of formula (XII).

Reaction scheme 2 HO TrocO OH OTroc HO protecting reaction HO, HO HO Õ O 0° O 3° 0 H O O can p R2 (Vil) Troc Troc R N O N/\, O Troc (IN OTES (Xll) Oyes coupling reaction 0 O 0 0 0 Ruz RUZ R2 HO O OH oh deprotecting reaction (VI) OUI o Ho o 0 In the above reaction scheme 2, each of Ru, R2 and R5 has the same meaning as defined above, Troc denotes 2,2,2-trichloroethoxycarbonyl and TES denotes triethylsily.

The novel taxaneterpine compound of formula (I) prepared according to the process of the present invention has a high water solubility and exhibits a superior anti-cancer activity, and therefore, can be used as a valuable anti-cancer agent. Thus, another purpose of the present invention is to provide an anti-cancer composition containing the compound of formula (I) as an active ingredient.

As mentioned above, in comparison to the prior taxane compounds the novel taxaneterpine compound of formula (I) according to the present invention not only exhibits a superior anti-cancer activity but also has a markedly improved water solubility. According to this, the compound of the present invention has the advantage in that it can be administered by formulating it into the desired preparation either using water only, but not using any solvent such as the mixture of ethanol and polyoxyethylcastor oil, which has been used in formulating the prior taxaneterpine compounds, or using the minimum amount of the solvent such as the mixture of ethanol and polyoxyethycastor oil, so that the side effects which may be caused by ethanol and polyoxyethyl- castor oil can be minimized.

Due to the improved water solubility, the anti-cancer compound of formula (I) according to the present invention can be formulated into an injectable preparation and effectively used in treating various cancerous diseases in the clinical field. As the injectable preparation, for example, aqueous or oily, sterilized injectable suspensions can be prepared using a suitable pharmaceutical carrier such as dispersing agents, wetting agents or suspending agents, according to the known method conventionally used in the pharmaceutical field. The aqueous solvent which can be used for this purpose includes pharmaceutically acceptable water, glucose solution, Ringer's solution or isotonic saline solution and further, a sterilized fixing oil can be commonly used as a solvent or a suspending medium.

In order to provide a sufficient anti-cancer activity in using the compound according to the present invention for the clinical purpose, a total daily dosage of the active compound is preferably in the range of 0.5mg to 50 mg per m'of body surface area. However, it should be understood that the unique dosage level for a specific patient can be appropriately adjusted by a person skilled in this art depending on the kind of the compound as used, weight, sex, health condition, diet, etc. of respective patient, administration time and method, excretion rate, combined drugs, or the kind and severity of cancer to be treated.

The present invention is more specifically explained by the following examples and experiments. However, it should be understood that these examples and experiments are provided for more clear understanding of the present invention but are not intended to limit the scope of the present invention thereto in any manner.

Example 1 Preparation of 10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxypaclitaxel 828mg (1 mmol) of 10-deacetyl-14 ß-hydroxypaclitaxel as prepared according to the method described in International Patent No. 94/03215 was dissolved in 10mQ of the mixed solvent of tetrahydrofuran and water in the ratio of 9: 1 (v/v). Nitrogen gas was then introduced into the resulting solution for 10 minutes and 50mQ of fresh samarium iodide (0.1M tetrahydrofuran solution) having a deep blue color, which was prepared by reacting samarium metal with iodine in tetrahydrofuran, was slowly added thereto. At this time, the color of the reaction solution was changed from deep blue to colorless.

When the color of the reaction solution is no longer changed, air was introduced into the solution for 10 minutes and 50mQ of 5% ammonium chloride solution was then added thereto. The reaction solution was extracted three times with ethyl acetate (100mQX3). The organic layer was washed two times with saturated sodium thiosulfate solution (100m x 2), dried over anhydrous magnesium sulfate and then distilled under reduced pressure to remove the organic solvent. The residue was purified with silica gel column chromatography [eluent: ethyl acetate/dichloromethane/methanol=50: 50: 3, v/v/v] to obtain 620mg (Yield: 75%) of the title compound.

Elementary analysis for C45HsiNOi4 Calculated C 65.61%; H N 1.69% Found C 65.62%; H N 1.68% lH-NMR (300MHz, acetone-d6) 8 (ppm) 1.20 (s, 3H, H17), 1.68 (s, 3H, H16), 1.73 (s, 3H, H19), 1.85 (s, 1H, OH), 2.04 (s, 3H, H18), 2.05 (b, 1H, OH), 2.09 (m, 1H, H6 ß), 2.40 (m, 1H, H6 cg), 2.48 (s, 3H, OAc), 3.16 (d, J=5.2Hz, 1H, H3), 3.98 (m, 1H, H7), 4.05 (d, 1H, H9), 4.18 (d, J=8. 0Hz, 1H, H20), 4.22 (d, J=8. 0Hz, 1H, H20 zy), 4.34 (m, 3H, 30H), 4.59 (m, 1H, H14), 4.91 (b, 1H, OH), 5.00 (m, 2H, H2'and H10), 5.15 (m, 1H, H5), 6.11 (m, 2H, H3'and H13), 6.29 (d, J=5.3Hz, 1H, H2), 7.42-7.68 (m, 11H), 7.96 (d, J=7. lHz, 2H), 8.17 (d, J=7. 1Hz, 2H), 8.36 (d, J=8.6Hz, 1H, NH) According to the procedure similar to that of Example 1, the title compounds of the following Examples 2 to 36 were prepared starting from the corresponding 10-deacetyl-14ß-hydroxytaxane derivatives of formula (VI).

Example 2 Preparation of 13-{(2R,3S)-3-benzoylamino-5-methyl-2-hydroxyhexanoyl}-10- deacetyl-9-deketo-9 ß, 14 -dihydroxybaccatin (ni) Yield: 78% Elementary analysis for C43H55NO14 Calculated C 65.51%; H 6. 21%; N 1.69% Found C 65.60%; H 6.19%; N 1.69% 'H-NMR (300MHz, acetone-d6) # (ppm) 0.99 (d, J=6.4Hz, 3H, CH3), 1.01 (d, J=6.5Hz, 3H, CH3), 1.21 (s, 3H, H17), 1.47 (m, 2H, CH2), 1.67 (s, 3H, H16), 1.70 (s, 3H, H19), 1.96 (s, 3H, H18), 1.96 (m, 2H, CHMe2 and H6 ß), 2.48 (m, 1H, H6a), 2.51 (s, 3H, OAc), 3.15 (d, J=5.3Hz, 1H, H3), 3.98 (m, 1H, <BR> <BR> <BR> H7), 4.02 (m, 1H, H3'), 4.18-4.34 (m, 6H, H9, H14, H20R, H20a and 20H), 4.45 (m, 1H, OH), 4.45 (m, 1H, OH), 4.59 (m, 2H, 20H), 5.12 (m, 2H, H10 and H2'), 5.23 (m, 1H, H5), 6.02 (d, J=6.8Hz, 1H, OH), 6. 26 (m, 2H, H2 and H13), 7.42-7.87 (m, 6H), 7.89 (d, J=7. 1Hz, 2H), 8.06 (d, J=8.6Hz, NH), 8.16 (d, J=7. 1Hz, 2H) Example 3 Preparation of 13-{(2R,3S)-3-benzoylamino-4-methyl-2-hydroxypentanoyl}-10- deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III) Yield: 70% Elementary analysis for C42H53NO14 Calculated C 63.38%; H N 1.76% Found C 63.21%; H 6.65%; N 1.70% 1H-NMR (300MHz, acetone-d6) (3 (ppm) 1.09 (d, J=6.7Hz, 3H, CH3), 1.23 (d, J=6.7Hz, 3H, CH3), 1.23 (s, 3H, H17), 1.68 (s, 3H, H16), 1.71 (s, 3H, H19), 1.82 (s, 3H, H18), 1.83 (m, 1H, H6 ß), 1.91 (m, 2H, CHMe2), 2.45 (m, 1H, H6a), 2.56 (s, 3H, OAc), 2.89 (b, 1H, OH), 3.11 (d, J=5.3Hz, 1H, H3), 3.97 (m, 1H, H7), 4.05 (m, 1H, H3'), 4. 22 (d, J=3.7Hz, 1H, H9), 4.25-4.35 (m, 4H, H20/3, <BR> <BR> <BR> H20 a and 20H), 4.40 (m, 2H, H14 and H2'), 4.72 (m, 1H, OH), 4.89 (b, 1H, OH), 5.14 (m, 1H, H5), 6.01 (d, J=6.5Hz, 1H, H13), 6.17 (d, J=3.3Hz, 1H, OH), 6.27 (d, J=5.4Hz, 1H, H2), 7.45-7.65 (m, 6H), 7.89 (d, J=7. 1Hz, 2H), 7.98 (d, J=7.8Hz, 1H, NH), 8.17 (d, J=7. 0Hz, 2H) Example 4 Preparation of 9-deketo-9 ß, 14 ß-dihydroxydocetaxel Yield: 80% Elementary analysis for C43H55NO15 Calculated C 62.53%; H 6.47%; N 1.69% Found C 62.51%; H 6.45%; N 1.64% H-NMR (300MHz, acetone-d6) # (ppm) 1.29 (s, 3H, H17), 1. 40 (s, 9H, CH3), 1.68 (s, 3H, H16), 1.75 (s, 3H, H19), 1.85 (s, 3H, H18), 1.88 (m, 1H, H6 /3), 2.42 (m, 1H, H6a), 2.44 (s, 3H, OAc), 2.91 (b, 1H, OH), 3.15 (d, J=5.3Hz, 1H, H3), 3.92 (m, 1H, H7), 4.05 (d, J=4. 0Hz, 1H, H9), 4.17 (d, J=7.9Hz, 1H, H20 ß), 4.24 (d, J=7.9Hz, 1H, H20 a), 4.33 (m, 3H, H14 and OH), 4.36 (m, 1H, H10), 4.78 (b, 2H, OH), 4.92 (m, 1H, H2'), 5.15 (m, 1H, H5), 5.41 (m, 1H, OH), 5.83 (d, J=3.9Hz, 1H, H3'), 5.83 (d, J=6.9Hz, 1H, H13), 6.29 (d, J=5.3Hz, 1H, H2), 6.72 (d, J=8.7Hz, 1H, NH), 7.32-7.63 (m, 8H), 8.13 (d, J=7. 2Hz, 2H) Example 5 Preparation of 13-{(2R, 3S)-3-(t-butoxyearbonyl) amino-5-methyl-2-hydroxy- hexanoyl}-10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III) Yield: 75% Elementary analysis for C41H59NO15 Calculated C 61.10%; H N 1.74% Found C 60.00%; H 7.25%; N 1.64% H-NMR (300MHz, CDCl3) # (ppm) 0.98 (d, J=7. 1Hz, 3H, CH3), 1.01 (d, J=7.3Hz, 3H, CH3), 1.29 (s, 3H, H17), 1.33 (m, 1H, CHMe2), 1.40 (s, 9H, CH3), 1.65 (s, 3H, H16), 1.70 (s, 3H, H19), 1.81 (s, 3H, H18), 1.86 (m, 3H, CH2 and H6 ß), 2.44 (s, 3H, OAc), 2.49 (m, 1H, H6 a), 3.15 (d, J=4.8Hz, 1H, OH), 4.02 (d, J=7.15Hz, 1H, H3), 4.06 (b, 1H, OH), 4.18-4.41 (m, 8H, H7, H9, H14, H20, H20 ß, H3', 20H), 4.63 (m, 1H, H5), 4.93 (d, J=8. 0Hz, 1H, H2'), 5.18 (m, 1H, OH), 5.82 (m, 2H, H10 and OH), 6.04 (d, J=6.6Hz, 1H, H2), 6.25-6.28 (m, 2H, H13 and NH), 7.52-7.65 (m, 3H), 8.15 (d, J=7.3Hz, 2H) Example 6 Preparation of 13-{(2R, 3S)-3-(t-butoxycarbonyl) amino-4-methyl-2-hydroxy- pentanoyl}-10-deacetyl-9-deketo-9 -dihydroxybaccatin(III)ß Yield: 60% Elementary analysis for C4oHs7NO1s Calculated C 60.67%; H 7.25%; N 1.77% Found C 60.67%; H 7.24%; N 1.75% 1H-NMR (300MHz, acetone-d6) 8 (ppm) 1.04 (d, J=6.7Hz, 3H, CH3), 1.13 (d, J=6.7Hz, 3H, CH3), 1.27 (s, 3H, H17), 1.43 (s, 9H, CH3), 1.68 (s, 3H, H16), 1.73 (s, 3H, H19), 1.83 (s, 3H, H18), 1.84 (m, 1H, H6 ß), 2.08 (m, 1H, CHMe2), 2.43 (s, 3H, OAc), 2.45 (m, 1H, H6 a), 2.89 (b, 1H, 20H), 3.08 (d, J=5.3Hz, 1H, H3), 3.83 (m, 1H, H7), 3.94 (m, 1H, H3'), 3.98 (d, J=3.6Hz, 1H, H9), 4.18 (d, J=8.3Hz, H20R), 4.22 (d, J=8.3Hz, H20a), 4.33 (m, 2H, OH), 4.46 (d, 2H, OH), 4.58 (m, 2H, H2'and OH), 4.94 (m, 1H, H10), 5.13 (m, 1H, H5), 5.81 (b, 1H, OH), 6.04 (d, J=7.2Hz, 1H, H13), 6.28 (d, J=5.3Hz, 1H, H2), 6.30 (d, J=8.6Hz, 1H, NH), 7.48-7.58 (m, 3H), 8.13 (d, J=7.2Hz, 2H) Example 7 Preparation of 13-{(2R, 3S)-3-(furyl-2-carbonyl) amino-5-methyl-2-hydroxyhexa- noyl}-10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III) Yield: 79% Elementary analysis for C41H53NO15 Calculated C 61.57%; H 6.68%; N 1.75% Found C H 6.70%; N 1.80% H-NMR (300MHz, acetone-d6) # (ppm) 0.96 (d, J=6.9Hz, 3H, CH3), 1.01 (d, J=6.9Hz, 3H, CH3), 1.23 (s, 3H, H17), 1.56 (m, 2H, CH2), 1.58 (s, 3H, H16), 1.71 (s, 3H, H19), 1.77 (m, 1H, CHMe2), 1.82 (s, 3H, H18), 1.88 (m, 1H, H6/3), 2.50 (s, 3H, OAc), 2.47 (m, 1H, H6 a), 2.83 (b, 1H, OH), 3.13 (d, J=5.4Hz, 1H, H3), 4.03 (m, 2H, H2 and H3'), 4.21 (d, J=3.8Hz, 1H, H9), 4.26-4.33 (m, 4H, H20 ß, H20 α and 20H), 4.45 (m, 1H, OH), 4.61 (m, 1H, H2'), 4.65 (d, d, J=6. 2Hz, H14), 4.90 (m, 2H, H10 and OH), 5.14 (m, 1H, H5), 6.03 (m, 2H, H13 and OH), 6.27 (d, J=5.4Hz, 1H, H2), 6.60 (dd, J=3.5Hz, J=1.7Hz, 1H), 7.14 (d, J=3.4Hz, 1H), 7.54-7.72 (m, 5H), 8.15 (d, J=7. 1Hz, 2H) Example 8 Preparation of 13-{(2R, 3S)-3-(furyl-2-carbonyl) amino-4-methyl-2-hydroxy- pentanoyl}-10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III) Yield: 66% Elementary analysis for C4oH5iNO15 Calculated C 61.14%; H 6.54%; N 1.78% Found C 61.11%; H 6.53%; N 1.64% 1H-NMR (300MHz, acetone-d6) # (ppm) 1.03 (d, J=6.57Hz, 3H, CH3), 1.21 (d, J=6.7Hz, 3H, CH3), 1.23 (s, 3H, H17), 1.67 (s, 3H, H16), 1.70 (s, 3H, H19), 1.76 (s, 3H, H18), 1.92 (m, 1H, H6/3), 2.30 (m, 1H, CHMe2), 2.46 (m, 1H, H6 a), 2.53 (s, 3H, OAc), 2.87 (b, 1H, OH), 3.10 (d, J=5.3Hz, 1H, H3), 3.99 (m, <BR> <BR> <BR> 1H, H7), 4.04 (m, 1H, H3'), 4.17-4.25 (m, 3H, H20ß, H20 a and H9), 4.32 (m, 2H, 20H), 4.52 (m, 1H, H14), 4.58 (m, 1H, H2'), 4.71 (b, 2H, 20H), 4.93 (m, 1H, H10), 5.13 (m, 1H, H5), 5.96 (d, J=3.7Hz, 1H, OH), 6.00 (d, J=6.9Hz, 1H, H13), 6.26 (d, J=5.4Hz, 1H, H2), 6.60 (dd, J=3.4Hz, J=1.7Hz, 1H), 7.14 (d, J=3.3Hz, 1H), 7.54-7.65 (m, 3H), 7.73 (d, J=1.7Hz, 1H), 7.76 (d, J=8.6Hz, 1H, NH), 8.15 (d, J=7. 1Hz, 2H) Example 9 Preparation of 13-{(2R, 3S)-3-(furyl-2-carbonyl) amino-3-phenyl-2-hydroxypro- pionyl}-10-deacetyl-9-deketo-9, 14 3-dihydroxybaccatin (III) Yield: 70% Elementary analysis for C43H49NO15 Calculated C 63.00%; H 6.02%; N 1.71% Found C 63.22%; H 5.99%; N 1.68% 'H-NMR (300MHz, acetone-d6) 3 (ppm) 1.23 (s, 3H, H17), 1.68 (s, 3H, H16), 1.70 (s, 3H, H19), 1.83 (s, 3H, H18), 1.89 (m, 1H, H6 ß), 2.43 (m, 1H, H6 a), 2.45 (s, 3H, OAc), 2.95 (b, 1H, OH), 3.15 (d, J=5.3Hz, 1H, H3), 3.95 (m, 1H, H7), 4.17 (d, 1H, J=8. 0Hz, H20/3), 4.22 (d, 1H, J=8. 0Hz, H20 a), 4.29-4.35 (m, 4H, 30H and H9), 4.59 (m, 1H, H14), 4.90-4.97 (m, 2H, H2'and H5), 5.12-5.17 (m, 2H, H10 and OH), 5.96 (bd, 1H, H3'), 6.04 (d, J=4.8Hz, 1H, OH), 6.11 (d, J=5.7Hz, 1H, H13), 6.29 (d, J=5.4Hz, 1H, H2), 6.61 (dd, J=3.4Hz, J=1.7Hz, 1H), 7.19 (d, J=3.4Hz, 1H), 7.32-7.65 (m, 8H), 7.75 (d, J=1.72Hz, 1H), 8.05 (d, J=9.5Hz, 1H, NH), 8.14 (d, J=7. 1Hz, 2H) Example 10 Preparation of 13-[(2R, 3S)-3-(t-butoxycarbonyl) amino-2-hydroxy-3-{(RS)-2- tetrahydrofuranyl} propionyl]-10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III) Yield: 65% Elementary analysis for C41H57NO16 Calculated C 60.06%; H 7.01%; N 1.71% Found C 60.00%; H 6.95%; N 1.76% 1H-NMR (300MHz, acetone-d6) 8 (ppm) 1.19 (s, 3H, H17), 1.34 (s, 9H, CH3), 1.36 (s, 3H, H16), 1.74 (s, 3H, H19), 1.80-2.18 (m, 5H), 1.88 (s, 3H, H18), 2.45 (s, 3H, OAc), 2.45 (m, 1H, H6 a), 2.88 (b, 2H), 3.79 (m, 1H, H7), 3.89 (m, 2H), 4.12-4.38 (m, 8H), 4.44 (m, 1H), 4.52 (d, J=5.6Hz, 1H, H2'), 4.64 (m, 1H), 4.95 (m, 1H, H5), 5.22 (m, 1H), 5.79 (m, 1H), 5.98 (d, J=5.3Hz, 1H, H2), 6.07 (1H, J=5.6Hz, H13), 6.43 (d, J=8.4,1H, NH), 7.50-7.65 (m, 3H), 8.10 (d, J=7. lHz, 2H) Example 11 Preparation of 13-{(2R, 3S)-3-benzoylamino-2-hydroxy-3-(2-furyl) propionyl}- 10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III) Yield: 69% Elementary analysis for C43H49NO15 Calculated C 63.00%; H 6.02%; N 1.71% Found C 62.87%; H 5.88%; N 1.77% 'H-NMR (300MHz, acetone-d6) 3 (ppm) 1.27 (s, 3H, H17), 1.39 (s, 9H, CH3), 1.67 (s, 3H, H16), 1.73 (s, 3H, H19), 1.83 (m, 1H, H6 ß), 1.83 (s, 3H, H18), 2.45 (s, 3H, OAc), 2.45 (m, 1H, H6 α), 3.16 (d, J=5.3Hz, 1H, H3), 4.05 (m, 2H), 4.18-4.35 (m, 5H), 4.56 (b, 1H), (m, 5H), 5.14 (m, 1H, H5), 6.08 (1H, J=5.5Hz, H13), 6.17 (m, 1H, H3'), 6.28 (d, J=5.3Hz, 1H, H2), 6.46 (dd, J=3.2Hz, J=1.7Hz, 1H), 6.61 (d, J=3.2Hz, 1H), 7.45-7.63 (m, 7H), 7.95 (d, J=7. 0Hz, 2H), 8.17 (d, J=7. 1Hz, 2H), 8.34 (b, 1H, NH) Example 12 Preparation of 13-{(2R, 3S)-3-(t-butoxycarbonyl) amino-2-hydroxy-3-(2-furyl)- propionyl}-10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III) Yield: 56% Elementary analysis for C41H53NO16 Calculated C 60.36%; H 6.55%; N 1.72% Found C 60.18%; H 6.72%; N 1.68% 1H-NMR (300MHz, acetone-d6) # (ppm) 1.27 (s, 3H, H17), 1.39 (s, 9H, CH3), 1.67 (s, 3H, H16), 1.73 (s, 3H, H19), 1.83 (m,-1H, H6 ß), 1.83 (s, 3H, H18), 2.45 (s, 3H, OAc), 2.45 (m, 1H, H6 a), 3.19 (d, J=5.3Hz, 1H, H3), 4.05 (m, 1H, H7), 4.11-4.32 (m, 4H), 4.61 (m, 1H), (m, 6H), 5.16 (m, 1H, H5), 5.46 (m, 1H), 5.78 (m, 1H), 6.07 (1H, J=5.5Hz, H13), 6.25 (d, J=5.3Hz, 1H, H2), 6.43 (dd, J=3.2Hz, J=1.7Hz, 1H), 6.48 (d, J=3.2Hz, 1H), 6.84 (d, J=8.4,1H, NH), 7.38-7.76 (m, 5H), 8.13 (d, J=7.0Hz, 2H) Example 13 Preparation of 13-{(2R, 3S)-3-(cyclopropylcarbonyl) amino-2-hydroxy-3-(2- furyl)propionyl}-10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III) Yield: 44% Elementary analysis for C4oH49NOis Calculated C 61.29%; H N 1.79% Found C 61.33%; H 6.22%; N 1.72% 'H-NMR (300MHz, acetone-d6) (ppm) 0.85-0.89 (m, 4H, cyclopropyl), 1.21 (s, 3H, H17), 1.62 (s, 3H, H16), 1.68 (s, 3H, H19), 1.83 (m, 1H, H6 ß), 1.83 (s, 3H, H18), 2.45 (s, 3H, OAc), 2.45 (m, 1H, H6 cr), 3.21 (d, J=5.4Hz, 1H, H3), 3.49 (m, 1H). 4.05 (m, 1H, H7), 4.21-4.35 (m, 6H), 4.46 (m, 1H), 4.82 (m, 1H), 4.97 (m, 1H, H5), 5.01 (b, 2H), 5.18 (m, 1H), 5.78 (m, 1H), 5.83 (m, 1H), 6.07 (1H, J=5.5Hz, H13), 6.25 (d, J=5.3Hz, 1H, H2), 6.51 (m, 2H), 6.84 (d, J=8.4, 1H, NH), 7.26-7.55 (m, 4H), 8.13 (d, J=7. 0Hz, 2H) Example 14 Preparation of 13-{(2R,3S)-3-benzoylamino-2-hydroxy-3-(2-thiophenyl) pro- pionyl}-10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III) Yield: 46% Elementary analysis for C43H49NO14S Calculated C 61.78%; H 5.91%; N 1.68%; S 3.84% Found C 61.52%; H 5.99%; N 1.70%; S 3.68% lH-NMR (300MHz, acetone-d6) 8 (ppm) 1.28 (s, 3H, H17), 1.64 (s, 6H, H16), 1.72 (s, 6H, H19), 1.84 (s, 3H, H18), 1.86 (m, 1H, H6 ß), 2.08 (b, 2H, OH), 2.45 (m, 1H, H6a), 2. 46 (s, 3H, OAc), 3.14 (d, J=5.3Hz, 1H, H3), 4.01 (m, 1H, H7), 4.16-4.33 (m, 5H), 4.46 (m, 1H), 4.56 (m, 1H), 4.73 (m, 1H), 4.91 (m, 1H), 5.14 (m, 1H, H5), 5.43 (m, 2H), 6.08 (d, J=6.5Hz, 1H, H13), 6.26 (m, 2H, H2 and H3'), 7.41-7.63 (m, 9H), 7.88 (d, J=7. 0Hz, 2H), 7.93 (d, J=8.3Hz, 1H, NH), 8.16 (d, J=7.2Hz, 2H) Example 15 Preparation of 13-{(2R,3S)-3-(t-butoxycarbonyl)amino-2-hydroxy-3-(2-thio- phenyl) propionyl}-10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III) Yield: 40% Elementary analysis for C41H53NO15S Calculated C 59.19%; H 6.42%; N 1.68%; S 3.85% Found C 59.30%; H 6.29%; N 1.71%; S 3.70% 1H-NMR (300MHz, acetone-d6) 8 (ppm) 1.32 (s, 3H, H17), 1.41 (s, 9H, CH3), 1.72 (s, 6H, H16 and H19), 1.84 (s, 3H, H18), 1.86 (m, 1H, H6R), 2.08 (b, 2H, OH), 2.38 (s, 3H, OAc), 2.38 (m, 1H, H6a), 2.95 (b, 1H, OH), 3.14 (d, J=5.3Hz, 1H, H3), 4.14-4.47 (m, 7H), 4.86 (d, J=3.5Hz, 1H, H3'), 5.00 (m, 1H, H2'), 5.23 (m, 1H, H5), 5.52 (m, 1H, OH), 5.69 (m, 2H), 6.04 (d, J=6.5Hz, 1H, H13), 6.25 (d, J=5.3,1H, H2), 7.05 (dd, J=3.5Hz, J=5. lHz, 1H), 7.23 (dd, J=0.9Hz, J=3.5Hz), 7.32 (dd, J=0.9Hz, J=5.1Hz, 1H), 7.49-7.63 (m, 3H), 8.17 (d, J=7.2Hz, 2H) Example 16 Preparation of 13-{(2R, 3S)-3-benzoylamino-2-hydroxy-5-methyl-4-hexenoyl}- 10-deacetyl-9-deketo-9 -dihydroxybaccatin(III)ß Yield: 42% Elementary analysis for C43H53NO14 Calculated C 63.93%; H N 1.73% Found C 63.87%; H 6.72%; N 1.83% 'H-NMR (300MHz, acetone-d6) # (ppm) 1.28 (s, 3H, H17), 1.67 (s, 3H, H16), 1.72 (s, 3H, H19), 1.79 (s, 3H, CH3), 1.81 (s, 3H, CH3), 1.86 (m, 1H, H6 , 8), 2.01 (s, 3H, H18), 2.08 (b, 2H, OH), 2.47 (s, 3H, OAc), 2.47 (m, 1H, H6 α), 3.15 (d, J=5.2Hz, 1H, H3), 3.62 (m, 2H), 3.97 (m, 1H, H7), 4.18-4.31 (m, 5H), 4.56 (b, 1H), 4.92 (m, 2H), 5.15 (m, 2H), 6.07 (d, J=6.2Hz, 1H, H13), 6.31 (m, 2H, H2 and H3'), 7.44-7.63 (m, 6H), 7.92 (d, J=7. 0Hz, 2H), 8.14 (d, J=7. lHz, 2H), 8.33 (d, J=8.3Hz, 1H, NH) Example 17 Preparation of 13-{(2R,3S)-3-(t-butoxycarbonyl)amino-2-hydroxy-5-methyl-4- hexenoyl}-10-deacetyl-9-deketo-9 -dihydroxybaccatin(III)ß Yield: 48% Elementary analysis for C4iHs7NOis Calculated C 61.26%; H N 1.74% Found C 61. 31% ; H 7.25%; N 1.68% IH-NMR (300MHz, acetone-d6) 3 (ppm) 1.30 (s, 3H, H17), 1.41 (s, 9H, CH3), 1.62 (s, 3H, H16), 1.72 (s, 3H, H19), 1.79 (s, 3H, CH3), 1.81 (s, 3H, CH3), 1.86 (m, 1H, H6 ß), 1.89 (s, 3H, H18), 2.08 (b, 2H, OH), 2.30 (s, 3H, OAc), 2.49 (m, 1H, H6 α), 2.92 (b, 1H, OH), (m, 8H), 4.96-5.01 (m, 3H), 5.64-5.68 (m, 2H), 6.04 (d, J=6.6Hz, 1H, H13), 6.25 (d, J=5.3Hz, 1H, H2), (m, 3H), 8.13 (d, J=7.2Hz, 2H) Example 18 Preparation of 13-{(2R, 3S)-3-(t-butoxycarbonyl) amino-2-hydroxy-3-(4-pyridyl)- propionyl}-10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III) Yield: 31% Elementary analysis for C42H54N2015 Calculated C 61.01%; H N 3.39% Found C 60.98%; H 6.67%; N 3.43% tH-NMR (300MHz, acetone-d6) a (ppm) 1.22 (s, 3H, H17), 1.33 (s, 9H, CH3), 1.67 (s, 6H, H16), 1.75 (s, 6H, H19), 1.82 (m, 1H, H6 ß), 1.98 (s, 3H, H18), 2.08 (b, 2H, OH), 2.32 (s, 3H, OAc), 2.52 (m, 1H, H6a), 3.17 (d, J=5.3Hz, 1H, H3), 4.02 (m, 1H, H7), 4.21-4.33 (m, 5H), 4.40 (m, 1H), 4.63 (m, 2H), 4.98 (m, 1H), 5.16 (m, 1H), 5.48 (m, 2H), 6.11 (d, J=6. 1Hz, 1H, H13), 6.26 (d, J=5.3Hz, 1H, H2), 6.35 (m, 1H, H3'), 7.37 (m, 2H), 7.43-7.65 (m, 3H), 8.09 (d, J=7. 1Hz, 2H), 8.67 (m, 2H) Example 19 Preparation of 10-deacetyl-9-deketo-9 ß,14 ß -dihydroxypaclitaxel-1, 14-carbo- nate Yield: 45% Elementary analysis for C46H47NOis Calculated C 64.55%; H 5.53%; N 1.64% Found C H N 1.71% 1H-NMR (300MHz, CDCl3) (ppm) 1.26 (s, 3H, H17), 1.66 (s, 3H, H16), 1.73 (s, 3H, H19), 1.85 (s, 1H, OH), 2.04 (s, 3H, H18), 2.05 (m, 1H, H6R), 2.22 (m, 1H, H6 α), 2.38 (s, 3H, OAc), 2.76 (d, J=5.2Hz, 1H, H3), 3.66 (b, 2H, OH), 3.88 (m, 1H, H7), 3.90 (d, J=8.4Hz, 1H, NH), 4.27 (m, 1H, H9), 4.28 (d, J=8.4Hz, 1H, H20), 4.35 (d, J=8.4Hz, 1H, H20 α), 4.58 (d, J=3.4Hz, 1H, OH), 4.68 (d, J=5.7Hz, 1H, H14), 4.82 (m, 1H, H2'), 5.00 (m, 1H, H5), 5.14 (m, 1H, H10), 5.88 (m, 1H, H3'), 6.32 (d, J=5.4Hz, 1H, H13), 6.52 (d, J=5.2Hz, 1H, H2), 7.32-7.62 (m, 11H), 7.80 (d, J=7.2Hz, 2H), 8.03 (d, J=7.2Hz, 2H) Example 20 Preparation of 13- { (2R, 3S)-3-benzoylamino-5-methyl-2-hydroxyhexanoyl}-10- ß-dihydroxybaccatin(III)-1,14-carbonatedeacetyl-9-deketo-9à Ÿ,14 Yield: 49% Elementary analysis for C44H53NO15 Calculated C 63.22%; H 6. 39%; N 1.68% Found C H 6.30%; N 1.71% H-NMR (300MHz, CDC13) # (ppm) 0.82 (d, J=5.9Hz, 3H, CH3), 0.84 (d, J=5.9Hz, 3H, CH3), 1.15 (s, 3H, H17), 1.41 (m, 2H, CH2), 1.46 (s, 3H, H16), 1.56 (s, 3H, H19), 1.64 (m, 2H, CHMe2 and H6), 1.72 (s, 3H, H18), 2.11 (m, 1H, H6 α), 2.26 (s, 3H, OAc), 2.63 (b, 1H, OH), 2.69 (d, J=5.3Hz, 1H, H3), 3.86 (m, 1H, H7), 3.98 (m, 1H, H3'), 4.04 (d, J=8.2Hz, 1H, H20), 4.13 (d, J=8.2Hz, 1H, H20 α), 4.27 (b, 1H, OH), 4.33 (d, J=3.2Hz, 1H, H2'), 4.43 (d, J=4.9Hz, 1H, H9), 4.56 (b, 2H, OH), 4.67 (d, J=5.9Hz, 1H, H14), 4.78 (d, J=5.6Hz, 1H, H10), 4.93 (m, 1H, H5), 5.27 (d, J=7.5Hz, NH), 6.20 (d, J=5.9Hz, 1H, H13), 6.31 (d, J=5.3Hz, 1H, H2), 7.21-7.44 (m, 6H), 7.67 (d, J=7. 1Hz, 2H), 7.85 (d, J=7.3Hz, 2H) Example 21 Preparation of 13-{(2R,3S)-3-benzoylamino-4-methyl-2-hydroxypentanoyl}-10- deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III)-1,14-carbonate Yield: 31% Elementary analysis for C43H51NO15 Calculated C 62.84%; H 6.25%; N 1.70% Found C 62.80%; H N 1.67% 'H-NMR (300MHz, acetone-d6) # (ppm) 1.08 (d, J=6.7Hz, 3H, CH3), 1.15 (d, J=6.7Hz, 3H, CH3), 1.25 (s, 3H, H17), 1.51 (s, 3H, H16), 1.60 (s, 3H, <BR> <BR> <BR> H19), 1.72 (s, 3H, H18), 1.85 (m, 1H, H6 ß), 2.24 (m, 2H, H6 a and CHMe2), 2.48 (s, 3H, OAc), 2.79 (d, J=5.2Hz, 1H, H3), 3.46 (b, 1H, OH), 3.56 (d, J=5.3Hz, 1H, OH), 3.84 (m, 2H, H3'and H7), 4.31-4.40 (m, 4H, H2', H9, H20 R and H20 a), 4.69 (b, 2H, OH), 4.78 (d, J=5.9Hz, 1H, H14), 5.02 (d, J=5.6Hz, 1H, H10), 5.17 (m, 1H, H5), 6.30 (d, J=5.9Hz, 1H, H13), 6.52 (d, J=5.2Hz, 1H, H2), 7.39-7.63 (m, 6H), 7.75 (d, J=7.2Hz, 2H), 8.06 (d, J=7.3Hz, 2H) Example 22 Preparation of 9-deketo-9 ß, 14 ß-dihydroxydocetaxel-1,14-carbonate Yield: 53% Elementary analysis for C44H53NO16 Calculated C 62.04%; H 6.27%; N 1.64% Found C 61.97%; H 6.32%; N 1.63% H-NMR (300MHz, CDC13) # (ppm) 1.35 (s, 3H, H17), 1.39 (s, 9H, CH3), 1.59 (s, 3H, H16), 1.72 (s, 3H, H19), 1.91 (s, 3H, H18), 1.85 (s, 1H, OH), <BR> <BR> <BR> 2.13 (m, 1H, H6 R), 2.28 (m, 1H, H6 a), 2.37 (s, 3H, OAc), 2.83 (d, J=5. 0Hz, 1H, H3), 2.87 (b, 1H, OH), 3.39 (b, 1H, OH), 3.54 (b, 1H, OH), 3.94 (m, 1H, H7), 4.09 (1H, OH), 4.29 (m, 1H, H9), 4.32 (d, J=8.4Hz, 1H, H20/3), 4.36 (d, J=8.4Hz, 1H, H20 a), 4.68 (d, J=5.7Hz, 1H, H14), 4.68 (m, 1H, H2'), 5.02 (m, 1H, H5), 5.29 (m, 1H, H10), 5.35 (d, J=9.8Hz, 1H, NH), 5.68 (m, 1H, H3'), 6.40 (d, J=5.4Hz, 1H, H13), 6.56 (d, J=5. 0Hz, 1H, H2), 7.32-7.65 (m, 8H), 8.03 (d, J=7. 1Hz, 2H) Example 23 Preparation of 13-{(2R,3S)-3-(t-butoxycarbonyl)amino-5-methyl-2-hydroxy- hexanoyl}-10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatinaII)-1,14-carbonate Yield: 48% Elementary analysis for C42H57NO16 Calculated C 60.64%; H N 1.68% Found C 60.57%; H 6.87%; N 1.72% H-NMR (300MHz, CDCl3) # (ppm) 0.90 (d, J=6.2Hz, 3H, CH3), 0.91 (d, J=6.2Hz, 3H, CH3), 1.29 (s, 3H, H17), 1.35 (s, 9H, CH3), 1.41 (m, 2H, CH2), 1.56 (s, 3H, H16), 1.63 (m, 1H, CHMe2), 1.76 (s, 3H, H19), 1.89 (s, 3H, H18), 1.90 (m, 1H, H6/3), 2.37 (s, 3H, OAc), 2.40 (m, 1H, H6 a), 2.97 (d, J=5.2Hz, 1H, H3), 3.24 (b, 1H, OH), 3.82 (m, 1H, H7), 4.03 (m, 1H, H3'), 4.07 (d, <BR> <BR> <BR> J=8. 0Hz, 1H, H20 ß), 4.18 (d, J=8. 0Hz, 1H, H20 a), 4. 25 (d, J=3.2Hz, 1H, H2'), 4.49 (d, J=5.5Hz, 1H, H9), 4.89 (b, 3H, OH), 4.90 (d, J=5.6Hz, 1H, H14), 4.93 (m, 1H, H5), 5.03 (d, J=5.5Hz, 1H, H10), 6.19 (d, J=9.6Hz, 1H, NH), 6.32 (d, J=5.6Hz, 1H, H13), 6.49 (d, J=5.3Hz, 1H, H2), 7.44-7.49 (m, 2H), 7.58-7.60 (m, 1H), 8.00 (d, J=7.3Hz, 2H) Example 24 Preparation of 13-{(2R, 3S)-3-(t-butoxycarbonyl) amino-4-methyl-2-hydroxypen- tanoyl}-10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III)-1,14-carbonate Yield: 34% Elementary analysis for C41H55NO16 Calculated C 60.21%; H 6.78%; N 1.71% Found C 60.24%; H 6.69%; N 1.68% 'H-NMR (300MHz, acetone-d6) # (ppm) 1.03 (d, J=6.7Hz, 3H, CH3), 1.08 (d, J=6.7Hz, 3H, CH3), 1.36 (s, 3H, H17), 1.42 (s, 9H, CH3), 1.71 (s, 3H, H16), 1.73 (s, 3H, H19), 1.84 (m, 1H, CHMe2), 1.90 (s, 3H, H18), 1.99 (m, 1H, H6 ß), 2.32 (m, 1H, H6 a), 2.43 (s, 3H, OAc), 2.85 (d, J=5. lHz, 1H, H3), 3.80 (b, 2H, OH), 3.80 (m, 1H, H7), 3.97 (m, 1H, H3'), 4.28 (d, J=8.2Hz, 1H, H20?), 4.35 (b, 2H, OH), 4.36 (d, J=8. 0Hz, 1H, H20 a), 4.57 (d, J=3. lHz, 1H, H2'), 4.75 (d, J=5.8Hz, 1H, H9), 4.98 (d, J=5.6Hz, 1H, H14), 5.01 (m, 1H, H5), 5.28 (d, J=5.8Hz, 1H, H10), 6.37 (d, J=5.6Hz, 1H, H13), 6.54 (d, J=5. 1Hz, 1H, H2), 7.46-7.51 (m, 2H), 7.60-7.65 (m, 1H), 8.04 (d, J=7.2Hz, 2H) Example 25 Preparation of 13-{(2R,3S)-3-(furyl-2-carbonyl)amino-5-methyl-2-hydroxyhexa - noyl}-10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (lII)-1,14-carbonate Yield: 51% Elementary analysis for C42H51NO16 Calculated C 61.08%; H 6.22%; N 1.70% Found C 61.11%; H 6.23%; N 1.65% 'H-NMR (300MHz, acetone-d6) S (ppm) 0.96 (d, J=6.9Hz, 3H, CH3), 0.99 (d, J=6.9Hz, 3H, CH3), 1.23 (s, 3H, H17), 1.42 (s, 2H, CH2), 1.54 (s, 3H, H16), 1.63 (s, 3H, H19), 1.67 (m, 1H, CHMe2), 1.70 (s, 3H, H18), 1.88 (m, 1H, H6/9), 2.53 (s, 3H, OAc), 2.60 (m, 1H, H6 a), 2.79 (d, J=5.7Hz, 1H, H3), <BR> <BR> <BR> 2.82 (b, 2H, OH), 3.81 (m, 1H, H7), 4.27-4.36 (m, 3H, H20 ß, H20 a and H3'), 4.43 (b, 1H, OH), 4.61 (d, J=6.0Hz, 1H, H9), 4.68 (m, 1H, H2'), 4.91 (d, J=5.5Hz, 1H, H14), 4.91 (b, 1H, OH), 5.05 (m, 1H, H5), 5.24 (d, J=6.9Hz, 1H, H10), 6.28 (d, J=5.5Hz, 1H, H13), 6.32 (d, J=5.7Hz, 1H, H2), 6.60 (dd, J=3.3Hz, J=1.7Hz, 1H), 7.08 (d, J=3.3Hz, 1H), 7.34 (d, J=8.4Hz, 1H, NH), 7.60-7.75 (m, 4H), 8.16 (d, J=7.2Hz, 2H) Example 26 Preparation of 13-{(2R, 3S)-3-(furyl-2-carbonyl) amino-4-methyl-2-hydroxypen- tanoyl}-10-deacetyl-9-deketo-9, 14 3-dihydroxybaccatin (III)-1,14-carbonate Yield: 43% Elementary analysis for C41H49NO16 Calculated C 60.66%; H 6.08%; N 1.73% Found C 60.64%; H 6.03%; N 1.75% H-NMR (300MHz, acetone-d6) d (ppm) 1.04 (d, J=6.9Hz, 3H, CH3), 1.15 (d, J=6.9Hz, 3H, CH3), 1.23 (s, 3H, H17), 1.53 (s, 3H, H16), 1.62 (s, 3H, H19), 1.68 (s, 3H, H18), 2.05 (m, 1H, CHMe2), 2.15 (m, 1H, H6 ß), 2.58 (m, 1H, H6 a), 2.60 (s, 3H, OAc), 2.82 (d, J=5.7Hz, 1H, H3), 2.89 (b, 2H, OH), 3.78 (m, 1H, H7), 4.30 (d, J=8.3Hz, 1H, H20 ß), 4.37 (d, J=8.3Hz, 1H, H20 a), 4.37 (b, 2H, OH), 4.41 (m, 1H, H3'), 4.78 (d, J=5.1Hz, 1H, H2'), 4.82 (b, 1H, OH), 4.90 (d, J=6.2Hz, 1H, H9), 4.98 (m, 2H, H5 and H14), 5. 28 (d, J=5. lHz, 1H, H10), 6.26 (d, J=5.5Hz, 1H, H13), 6.30 (d, J=5.7Hz, 1H, H2), 6.51 (d, J=5.7Hz, 1H, H2), 6.51 (dd, J=3.4Hz, J=1.7Hz, 1H), 7.07 (d, J=3.4Hz, 1H), 7.32 (d, J=8.4Hz, 1H, NH), 7.62-7.74 (m, 4H), 8.16 (d, J=7.2Hz, 2H) Example 27 Preparation of 13-{(2R, 3S)-3-(furyl-2-carbonyl) amino-3-phenyl-2-hydroxypro- pionyl}-10-deacetyl-9-deketo-9 , 14 ß-dihydroxybaccatin (III)-1, 14-carbonate Yield: 52% Elementary analysis for C44H47NO16 Calculated C 62.48%; H 5.84%; N 1.66% Found C H 5. 71%; N 1.60% 1H-NMR (300MHz, acetone-d6) 8 (ppm) 1.23 (s, 3H, H17), 1.66 (s, 3H, H16), 1.68 (s, 3H, H19), 1.92 (m, 1H, H6b), 1.97 (s, 3H, H18), 2.47 (m, 1H, H6a), 2.47 (s, 3H, OAc), 3.34 (d, J=5.4Hz, 1H, H3), 3.91 (m, 1H, H7), 4.10 (d, J=7.9Hz, 1H, H20b), 4.17 (d, J=7.9Hz, 1H, H20a), 4.32 (d, J=4. 0Hz, 1H, OH), 4.46 (d, J=6.7Hz, 1H, H9), 4.63 (m, 2H, OH and H2'), 4.90 (d, J=6. lHz, 1H, H14), 5.00 (m, 2H, H5 and H10), 5.12 (m, 1H, OH), 5.56 (bd, 1H, OH), 5.77 (dd, J=4. 0Hz, J=8.9Hz, 1H, H3'), 6.37 (d, J=6. lHz, 1H, H13), 6.58 (d, J=5.4Hz, 1H, H2), 6.62 (dd, J=3.4Hz, J=1.7Hz, 1H), 7.13 (d, J=3.4Hz, 1H), 7.57-7.75 (m, 9H), 7.96 (d, J=8.9Hz, 1H, NH), 8.11 (d, J=7.2Hz, 2H) Example 28 Preparation of 13-[(2R,3S)-3-(t-butoxycarbonyl)amino-2-hydroxy-3-{(RS)-2- tetrahydrofuranyl} propionyl]-10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III)-1,14-carbonate Yield: 63% Elementary analysis for C42H5sNOl7 Calculated C 59.64%; H 6.55%; N 1.66% Found C 59.26%; H 6.60%; N 1.65% H-NMR (300MHz, acetone-d6) # (ppm) 1.21 (s, 1H, H17), 1.36 (s, 9H, CH3), 1.38 (s, 3H, H16), 1.74 (s, 3H, H19), 1.80-2.18 (m, 5H), 1.88 (s, 3H, H18), 2.45 (s, 3H, OAc), 2.45 (m, 1H, H6 α), 2.87 (d, J=5.2Hz, 1H, H3), 3.79 (m, 1H, H7), 3.94 (m, 2H), 4.12 (d, J=8. 0Hz, 1H, H20 cr), 4.20-4.38 (m, 6H), 4.44 (m, 1H), 4.52 (d, J=5.6Hz, 1H, H2'), 4.64 (m, 1H), 4.95 (m, 1H, H5), 5.22 (m, 1H), 5.67 (m, 1H), 5.79 (m, 1H), 6.36 (1H, J=5.6Hz, H13), 6.54 (d, J=5.3,1H, H2), 7.45-7.65 (m, 3H), 8.05 (d, J=7.2Hz, 2H) Example 29 Preparation of 13-{(2R, 3S)-3-benzoylamino-2-hydroxy-3-(2-furyl) propionyl}-10- deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III)-1,14-carbonate Yield: 58% Elementary analysis for C44H47NO16 Calculated C 62.48%; H 5.60%; N 1.66% Found C 62.80%; H 5.60%; N 1.65% H-NMR (300MHz, acetone-d6) 8 (ppm) 1.33 (s, 3H, H17), 1.68 (s, 6H, H16), 1.72 (s, 6H, H19), 1.84 (m, 1H, H6 a), 2.04 (s, 3H, H18), 2.45 (m, 1H, H6 a), 2.50 (s, 3H, OAc), 2.78 (m, 1H), 3.05 (d, J=5.4Hz, 1H, H3), 3.08 (b, 1H, OH), 3.91 (m, 1H, H7), 4.15 (d, J=7.9Hz, 1H, H20), 4.25 (d, J=7.9Hz, 1H, H20 α), 4.25 (m, 1H), 4.42 (m, 1H), 4.63 (d, J=6. 1Hz, 1H, H14), 4.97 (m, 2H), 5.04 (d, J=4.7Hz, 1H, H2'), 5.12 (d, J=5.4Hz, 1H, H10), 5.48 (m, 1H), 5.93 (m, 1H, H3'), 6.42 (m, 2H, H13 and furan), 6.48 (d, J=3.2Hz, 1H), 6.55 (d, J=5.4, 1H, H2), 7.45-7.70 (m, 7H), 8.00 (m, 1H, NH), 8.00 (d, J=7. lHz, 2H), 8.12 (d, J=7.2Hz, 2H) Example 30 Preparation of 13-{(2R,3S)-3-(t-butoxycarbonyl)amino-2-hydroxy-3-(2- furyl) propionyl}-10-deacetyl-9-deketo-9 6,14 ß-dihydroxybaccatin (III)-1,14- carbonate Yield: 65% Elementary analysis for C42H5iNO17 Calculated C 59.92%; H 6.11%; N 1.66% Found C 60.03%; H 6.06%; N 1.75% 'H-NMR (300MHz, acetone-d6) # (ppm) 1.36 (s, 3H, H17), 1.46 (s, 9H, CH3), 1.69 (s, 6H, H16), 1.72 (s, 6H, H19), 1.84 (m, 1H, H6 ß), 1.91 (s, 3H, H18), 2.35 (m, 1H, H6 α), 2.40 (s, 3H, OAc), 2.73 (m, 1H), 2.85 (d, J=5.3Hz, 1H, H3), 3.42 (m, 1H), 3.49 (m, 1H), 3.98 (m, 1H, H7), 4.07 (m, 1H), 4.30 (m, 1H), 4.30 (d, J=8.2Hz, 1H, H20R), 4.37 (d, J=8.2Hz, 1H, H20 a), 4.74 (m, 2H), 5.00 (m, 1H), 5.31 (m, 1H), 5.41 (m, 2H), 6.34-6.39 (m, 3H, H13 and furan), 6.48 (d, J=3.2Hz, 1H), 6.54 (d, J=5.3,1H, H2), 7.27 (m, 1H), 7.41-7.62 (m, 3H), 8.04 (d, J=7.3Hz, 2H) Example 31 Preparation of 13-{(2R, 3S)-3-(cyclopropylcarbonyl) amino-2-hydroxy-3-(2- furyl) propionyl}-10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III)-1, 14- carbonate Yield: 48% Elementary analysis for C41H47NO16 Calculated C 60.81%; H 5.85%; N 1.73% Found C 60.96%; H 5.76%; N 1.72% 1H-NMR (300MHz, acetone-d6) 8 (ppm) 0.72 (m, 2H, cyclopropyl), 0.83 (m, 2H, cyclopropyl), 1.35 (s, 3H, H17), 1.68 (s, 6H, H16), 1.79 (s, 6H, H19), 1.84 (m, 1H, H6R), 2.05 (s, 3H, H18), 2.47 (m, 1H, H6 α), 2.49 (s, 3H, OAc), 2.85 (b, 1H), 2.85 (d, J=5.5Hz, 1H, H3), 3.93 (m, 1H, H7), 4.13 (d, <BR> <BR> <BR> J=8. 0Hz, 1H, H20 ß), 4.23 (d, J=8. 0Hz, 1H, H20a), 4.30 (d, J=4. lHz, 1H, OH), 4.43 (d, J=6.8Hz, 1H, OH), 4.58 (d, J=5. lHz, 1H, H9), 4.65 (m, 1H, H2'), 4.90-4.98 (m, 3H), 5.20 (m, 1H, H5), 5.36 (d, J=5.2Hz, 1H, H10), 5.67 (m, 1H), 6.36-6.39 (m, 3H, H13 and furan), 6.57 (d, J=5.4Hz, 1H, H2), 7.51-7.78 (m, 5H), 8.10 (d, J=7.7Hz, 2H) Example 32 Preparation of 13-{(2R,3S)-3-benzoylamino-2-hydroxy-3-(2-thiophenyl) pro- pionyl}-10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III)-1,14-carbonate Yield: 53% Elementary analysis for C44H47NOisS Calculated C 61.32%; H 5.60%; N 1.66% ; S 3.72% Found C 61.20%; H 5.60%; N 1.65%; S 3.86% 1H-NMR (300MHz, acetone-d6) # (ppm) 1.29 (s, 3H, H17), 1.67 (s, 6H, H16 and H19), 1.86 (m, 1H, H6 ß), 1.93 (s, 3H, H18), 1.96 (b, 2H, OH), 2.46 (m, 1H, H6 α), 2.51 (s, 3H, OAc), 3.08 (d, J=5.3Hz, 1H, H3), 3.86 (m, 1H, H7), 4.16 (d, J=8. 0Hz, 1H, H20), 4.24 (d, J=8. 0Hz, 1H, H20 α), 4.28 (m, 1H), 4.39 (m, 1H), 4.55 (m, 1H), 4.62 (m, 1H), 4.95 (m, 2H), 5.02 (m, 1H), 5.13 (m, 1H), 5.65 (d, J=5.8Hz, 1H), 6.09 (dd, J=3.9Hz, J=8.7Hz, 3'H), 6.38 (1H, J=5.8Hz, H13), 6.58 (d, J=5.1,1H, H2), 7.26 (dd, J=l. lHz, J=3.4Hz, 1H), 7.39 (dd, J=l. lHz, J=5. 1Hz), 7.46-7.70 (m, 6H), 7.95 (d, J=7.6Hz, 2H), 8.09 (d, J=7.7Hz, 2H) Example 33 Preparation of 13-{(2R, 3S)-3-(t-butoxycarbonyl) amino-2-hydroxy-3-(2-thio- phenyl) propionyl}-10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III)-1,14- carbonate Yield: 49% Elementary analysis for C42H51NO16S Calculated C 58.80%; H 5.99%; N 1.63%; S 3.74% Found C 58. 60%; H 6.11%; N 1.65%; S 3.82% H-NMR (300MHz, acetone-d6) # (ppm) 1.30 (s, 3H, H17), 1.43 (s, 9H, CH3), 1.72 (s, 6H, H16 and H19), 1.84 (s, 3H, H18), 1.86 (m, 1H, H6), 2.38 (m, 1H, H6a), 2.41 (s, 3H, OAc), 2.83 (d, J=5.2Hz, 1H, H3), 3.08 (b, 1H, OH), 3.52 (b, 1H, OH), 3.70 (m, 1H, H7), 3.93 (m, 1H, OH), 4.30 (d, J=8.8Hz, <BR> <BR> <BR> 1H, H20 ß), 4.38 (d, J=8.8Hz, 1H, H20a), 4.29-4.39 (m, 2H), 4.72 (m, 2H), 5.02 (m, 1H), 5.26 (m, 1H), 5.57 (m, 2H), 6.38 (d, J=5.6Hz, H13), 6.55 (d, J=5.3Hz, 1H, H2), 7.00 (dd, J=3.5Hz, J=5. 1Hz, 1H), 7.12 (dd, J=0.9Hz, J=3.5Hz), 7.28 (m, 1H), 7.46-7.65 (m, 3H), 8.05 (d, J=7.7Hz, 2H) Example 34 Preparation of 13-{(2R,3S)-3-benzoylamino-2-hydroxy-5-methyl-4-hexenoyl}- 10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III)-1,14-carbonate Yield: 60% Elementary analysis for C44H51NO15 Calculated C 63.38%; H 6.16%; N 1.68% Found C 63.29%; H 6.09% ; N 1.53% 'H-NMR (300MHz, acetone-d6) # (ppm) 1.34 (s, 3H, H17), 1.67 (s, 6H, H16), 1.76 (s, 3H, CH3), 1.77 (s, 6H, H19), 1.80 (s, 6H, CH3), 1.85 (m, 1H, H6 R), 1.97 (s, 3H, H18), 2.44 (m, 1H, H6 α), 2.49 (s, 3H, OAc), 2.78 (b, 1H), 3.03 (d, J=5.4Hz, 1H, H3), 3.90 (m, 1H, H7), 4.13 (d, J=8. 0Hz, 1H, H20ß), 4.22 (d, J=8. 0Hz, 1H, H20 α), 4.26 (m, 1H), 4.36 (m, 1H), 4.62 (m, 3H), 4.95 (m, 2H), 5.30 (m, 2H), 5.48 (m, 1H), 6.38 (d, J=6. 1Hz, 1H, H13), 6.57 (d, J=5.4Hz, 1H, H2), 7.45-7.69 (m, 6H), 8.78 (d, J=8.4Hz, 1H, NH), 7.92 (dd, J=7. 0Hz, J=1.5Hz, 2H), 8.07 (d, J=7.7Hz, 2H) Example 35 Preparation of 13-{(2R,3S)-3-(t-butoxycarbonyl)amino-2-hydroxy-5-methyl-4- <BR> <BR> <BR> hexenoyl}-10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III)-1,14-carbonate Yield: 66% Elementary analysis for C42H55NO16 Calculated C 60.79%; H 6.68%; N 1.69% Found C 60.85%; H 6.72%; N 1.56% 'H-NMR (300MHz, acetone-d6) 8 1.30 (s, 3H, H17), 1.41 (s, 9H, CH3), 1.62 (s, 3H, H16), 1.72 (s, 3H, H19), 1.79 (s, 3H, CH3), 1.81 (s, 3H, CH3), 1.86 (m, 1H, H6 ß), 1.89 (s, 3H, H18), 2.08 (b, 2H, OH), 2.30 (s, 3H, OAc), 2.49 (m, 1H, H6 α), 2.92 (b, 1H, OH), 4.14-4.47 (m, 8H), 4.96-5.01 (m, 3H), 5.64-5.68 (m, 2H), 6.04 (d, J=6.6Hz, 1H, H13), 6.25 (d, J=5.3,1H, H2), 7.38-7.61 (m, 3H), 8.13 (d, J=7.2Hz, 2H) Example 36 Preparation of 13-{(2R, 3S)-3-(t-butoxycarbonyl) amino-2-hydroxy-3-(4- pyridyl) propionyl}-10-deacetyl-9-deketo-9 ß, 14 ß-dihydroxybaccatin (III)-1,14- carbonate Yield: 39% Elementary analysis for C43H52N2016 Calculated C 60.56%; H 6.15%; N 3.28% Found C 60.33%; H 6.09%; N 3.20% 1H-NMR (300MHz, acetone-d6) a (ppm) 1.56 (s, 3H, H17), 1.62 (s, 9H, CH3), 1.90 (s, 6H, H16), 2.02 (s, 6H, H19), 2.15 (m, 1H, H6 ß), 2 20 (s, 3H, <BR> <BR> <BR> H18), 2.49 (m, 1H, H6 a), 2.67 (s, 3H, OAc), 3.27 (d, J=5.3Hz, 1H, H3), 4.14 (m, 1H, H7), 4.36 (d, J=7.9Hz, 1H, H20), 4.45 (d, J=7.9Hz, 1H, H20 cg), 4.52 (m, 1H), 4.64 (m, 1H), 4.80 (m, 1H), 4.86 (m, 1H), 5.11-5.20 (m, 3H), 5.20 (d, 1H, J=5.3Hz), 5.48 (m, 1H), 6.60 (d, J=6. lHz, 1H, H13), 6.76 (m, 1H, H3'), 6.80 (d, J=5.3Hz, 1H, H2), 7.71 (m, 2H), 7.73-7.92 (m, 3H), 8.30 (d, J=7.1Hz, 2H), 8.80 (m, 2H) Expriment 1: Determination of in vitro anti-cancer activity The anti-cancer activity of the compound of formula (I) according to the present invention was determined by the known in vitro sulforhodamine B (SRB) method [see, P. Skehan, et al., New colorimetric cytotoxic assay for anti-cancer drug screening, J. Natl. Cancer Inst., 1990,82,1107-1112] as described below.

In this experiment, A549 (human lung cancer cell line), HCT15 (human colon cancer cell line), SKOV-3 (human ovarian cancer cell line), XF498 (human CNS cancer cell line) and SK-MEL-2 (human melanoma cell line) were used as the test cancer cell lines, and paclitaxel (Table) was used as the comparative compound.

Each test cancer cell line was incubated with RPMI1640 medium (Sigma) for 48 hours in an incubator at 37°C in the presence of 5% CO2.

The test compounds and paclitaxel as the comparative compound were prepared in the concentration of lmg/mQ using dimethylsulfoxide (DMSO) and then added to the plate with gradually diluting with DMSO in 10-fold dilution scale and incubated for further 48 hours. Then, the culture medium was removed.

50% Trichloroacetic acid (TCA) was added to the plate in an amount of 50fa per well at 4°C to fix the cells for one hour (final concentration 10%). After removing TCA, the plate was washed with distilled water and dried, and 0.4% sulforhodamine B (SRB) dissolved in 1% acetic acid as the dyeing solution was added to the plate in an amount of 50gui per well. After 20 minutes, sulforhodamine B was removed and the plate was then washed four times with 1% acetic acid solution and dried. 10mmol/Q non-buffered tris base {tris- (hydroxymethyl) aminomethane} was added to the plate in an amount of 150 per well and then thoroughly mixed together. Then, the absorbance of each well was measured at 540nm, from which the concentration of the active compound to inhibit the growth of cancer cells by 50% as the anti-cancer activity (ED50) was calculated by means of a microplate reader. On the basis of the ED50 values as calculated, the ratio of the anti-cancer activity of the test compound according to the present invention to that of paclitaxel as the comparative compound was calculated and described in the following Table 1.

Table 1 In vitro anti-cancer activity of the compound of formula (I) according to the present invention (cytotoxicity: EDSO of the test compound/EDso of paclitaxel) Kind of cancer cells CompoundNo. A549 SKOV-3 SK-MEL-2 HCT 15 XF498 Paclitaxel 1 1 1 1 Example4 2 10 19. 8 0. 63 4.5 Example5 9 0. 1 262 3. 78 1.1 Example6 4 8. 2 5. 5 3. 1 1.0 Example 7 0.43 32. 7 20 47. 5 6.5 Example8 23. 4 1. 3 16 21. 9 70.9 Example11 45 2. 5 2. 7 2. 0 8.57 Example14 1. 7 1. 0 0. 5 1. 9 1.7 Example15 1. 3 15. 1 2. 0 1. 8 18.6 Example16 1 1 Example17 1. 9 1. 4 1. 6 2. 1 5.5 Example18 2. 2 1. 0 1. 6 0. 9 1.9 Example19 70 21. 7 41. 3 2 >0.8 Example20 1. 6 1. 4 1. 9 >3. 3 1.8 Example23 0. 2 0. 1 1. 2 2. 0 0.3 Example24 0. 3 1. 2 1. 0 2. 1 0.7 Example25 0. 25 0. 05 20 53. 6 3.0 Example27 15. 7 15. 8 10 3. 4 2.1 Example29 1. 8 1. 2 0. 9 4. 4 1.8 Example30 1. 3 1. 2 1. 6 1. 2 1.6 Example31 12. 9 5. 1 8. 8 2. 8 8.4 Example32 1. 2 0. 9 0. 7 2. 0 1.9 Example33 1. 5 13. 3 3. 3 1. 0 10.9 Example34 1. 7 0. 9 0. 9 0. 7 1.8 Example35 1. 7 9. 6 1. 3 2. 7 18.7 Example36 0. 8 0. 8 1. 3 0. 3 0.9 Note 1. Cell lines: A549 (human lung cancer cell line), HCT15 (human colon cancer cell line), SKOV-3 (human ovarian cancer cell line), XF498 (human CNS cancer cell line), SK-MEL-2 (human melanoma cell line) 2. Measuring method: SRB (sulforhodamine B) assay As can be seen from the result described in the above Table 1, the anti-cancer active compound according to the present invention exhibits equivalent or more superior anti-cancer activity in comparison to paclitaxel as the comparative compound. Therefore, it can be noted that the compound of the present invention can be effectively used as an anti-cancer agent.

Experiment 2: Determination of water solubility The compound of formula (I) according to the present invention has a markedly improved water solubility in comparison to the prior taxane compounds. In order to confirm the improved water solubility, the standard solution and the test solution were prepared according to the method described below and then the water solubility of each test compound was measured by high performance liquid chromatography (HPLC).

-Preparation of the standard solution 5mg of the test sample was precisely weighed and dissolved in 10mQ of methanol to prepare the standard solution. Simultaneously with the preparation of the standard solution, the solution of paclitaxel was also prepared according to the same manner.

-Preparation of the test solution The test sample was dissolved in the given amount of water and then vigorously shaken at intervals of 5 minutes for 30 minutes to make the saturated solution. The undissolved test sample was filtered off through 0.45 , am semipermeable membrane to prepare the test solution. Simultaneously with the preparation of the test solution, the aqueous solution of paclitaxel as the comparative compound was also prepared according to the same manner.

-Conditions of HPLC analysis 1) Eluent: 50%-65% aqueous acetonitrile solution 2) Column: Capcell-pak C18 4.6 x 150mm 3) Detector: UV 235nm 4) Flow rate: 1.5m/min.

5) Injection amount: 10µl 6) Calculating method: The rate of HPLC area of the test sample/ HPLC area of the standard solution at the given concentration in mg/m. was calculated to determine the water solubility and the obtained results are described in the following Table 2.

Table 2 Water solubility of the novel taxaneterpine compound of formula (I) according to the present invention Compound of the present Compound No. Solubility invention/Paclitaxel 1Paclitaxel0.0008mg/ml Docetaxel 11 Example 1640.1315mg/ml Example 2 0. 0536mg/mQ 67 Example 3 0. 2060mg/mQ 258 Example 4 0. 1237mg/mQ 157 Example 50. 0550mg/m69 Example 2770.2214mg/ml Example 1570.1252mg/ml Example 3830.3060mg/ml Example 1890.1514mg/ml Example 1870.1122mg/ml Example 900.0721mg/ml Example 1400.1124mg/ml Example 760.0456mg/ml Example 300.0179mg/ml Table 2 (continued) of the present Compound No. Solubility invention/Paclitaxel Example 320.0252mg/ml Example 110.0084mg/ml Example 21 0. 0348mg/mQ 44 Example 710.0564mg/ml Example 23 0. 0330mg/mt 41 Example 910.0726mg/ml Example 190.0152mg/ml Example 690.0555mg/ml Example 340.0135mg/ml Example 28 0. 0300mg/mQ 50 Example 430.0342mg/ml Example 700.0562mg/ml Example 700.0562mg/ml Example 32 0. 1403mg/mQ 175 Example 330. 0025mg/n4 Example 380.0303mg/ml Example 35 0. 0217mg/mQ 36 As can be seen from the results described in the above Table 2, the compound of formula (I) according to the present invention in which the 9-ketone group is reduced to hydroxy group shows a markedly high water solubility which is 4 to 383 times and up to 35 times as large as paclitaxel and docetaxel, respectively.

For reference, in order to prove that the water solubility can be increased by reducing the 9-ketone group to hydroxy group, the water solubilities of the typical compounds (Examples 1,4,19 and 22) among the 9 ß-hydroxytaxaneterpine compound of formula (I) according to the present invention were compared with those of the corresponding starting compounds of formula (VI), i. e. the taxaneterpine compounds having the unreduced 9-ketone group. The solubility was measured according to the same manner as above and the results are described in the following Table 3.

Table 3 Comparison of the water solubility of the compound of formula (I) according to the present invention with that of the corresponding compound of formula (VI) having 9-keto group Compound of formula (VI) Compound of formula (I) corresponding to compound Solubility of (9 ß -hydroxy derivative) of formula (1) compound (I) (9-keto derivative)/Solubility of compound(VI Solubility Solubility No. Example 1 0.1315mg/ 0. 0112mg/ 11.7 Example 4 0. 1237mg/ml 0.0151 mg/mQ 8.2 Example 19 0. 0564mg/ml 0. 0036mg/ml 15.7 Example 22 0. 0252mg/ 0.0057mg/mQ 4.4 From the results described in the above Table 3, it can be noted that the 9?-hydroxy compound of formula (I) according to the present invention shows an increase in the water solubility by 4 to 16 times in comparison to the 9-keto derivative.

Due to such increased water solubility, the compound of formula (I) according to the present invention can be administered to human patients with many advantages. Specifically, in practically using paclitaxel in the clinical field, paclitaxel can be administered in the form of an injectable solution prepared by dissolving paclitaxel in the mixed solvent of 50% ethanol and 50% polyoxyethylcastor oil and then diluting the resulting solution with 5% injectable glucose solution, 0.9% injectable sodium chloride solution, 5% injectable glucose solution and 0.9% injectable sodium chloride solution, or 5% injectable glucose Ringer's solution in the concentration of . .

However, in consideration of the fact that the single dosage of paclitaxel for human adult having 60kg body weight as proposed by FDA is 170 to 300mg, the compound of formula (I) according to the present invention provides the advantage that it can be directly dissolved in 5% injectable glucose solution, 0.9% injectable sodium chloride solution, 5% injectable glucose solution and 0.9% injectable sodium chloride solution, or 5% injectable glucose Ringer's solution without using the mixed solvent of 50% ethanol and 50% polyoxyethylcastor oil to prepare the injectable preparation for use in the clinical field.

As mentioned above, the present invention provides the novel taxaneterpine compound of formula (I) which is prepared by reducing a ketone group present in the 9-position of 14 ß-hydroxytaxaneterpine structure to a hydroxy group such that dihydroxy groups are introduced into both the 9?- and 14 ß-positions of taxaneterpine structure. This compound exhibits a superior anti-cancer activity and further shows a markedly improved water solubility in comparison to the prior taxaneterpine compounds. The anti-cancer activity and improved water solubility of the compound according to the present invention were identified through the above Experiments 1 and 2.

Therefore, the novel taxaneterpine compound of formula (I) according to the present invention can achieve the apparent progress in the relevant pharmaceutical technical field by improving both the problems related to the sparing solubility of the prior taxaneterpine anti-cancer compounds in water and to the side effects in the clinical field due to such sparing water solubility.