MACROCYCLIC PICOLINAMIDES AS FUNGICIDES

BACKGROUND & SUMMARY

[0001] Fungicides are compounds, of natural or synthetic origin, which act to protect and/or cure plants against damage caused by agriculturally relevant fungi. Generally, no single fungicide is useful in all situations. Consequently, research is ongoing to produce fungicides that may have better performance, are easier to use, and cost less.

[0002] The present disclosure relates to macrocyclic picolinamides and their use as fungicides. The compounds of the present disclosure may offer protection against ascomycetes, basidiomycetes, deuteromycetes and oomycetes.

[0003] One embodiment of the resent disclosure may include compounds of Formula I:

wherein

X is H or C(0)R ₂ ;

Y is H, C(0)R ₂ , or Q;

Q is

Ri is independently selected from the group consisting of alkyl, alkenyl, aryl, cycloalkyl, heterocycle, and C(0)Rs, each optionally substituted with 0, 1 or multiple

Rs;

R ₂ is alkyl or alkoxy, each optionally substituted with 0, 1, or multiple R5; R3 is selected from the group consisting of hydrogen and alkoxy; R ₄ is hydrogen, -C(0)R ₆ , or -CH ₂ OC(0)R ₆ ;

R5 is hydrogen, alkyl, alkenyl, alkoxy, aryl, arylalkoxy, cycloalkyl, halo, haloalkyl, or haloalkoxy;

R ₆ is alkyl or alkoxy, each optionally substituted with 0, 1, or multiple R7;

R7 is hydrogen, alkyl, aryl, halo, acyloxy, alkenyl, alkoxy, heteroaryl, heterocycle, or thioalkyl, each optionally substituted withO, 1, or multiple R _8;

R ₈ is hydrogen, alkyl, haloalkyl, alkoxy, haloalkoxy, aryl, or halo.

[0004] Another embodiment of the present disclosure may include a fungicidal composition for the control or prevention of fungal attack comprising the compounds described above and a phytologically acceptable carrier material.

[0005] Yet another embodiment of the present disclosure may include a method for the control or prevention of fungal attack on a plant, the method including the steps of applying a fungicidally effective amount of one or more of the compounds described above to at least one of the fungus, the plant, and an area adjacent to the plant.

[0006] It will be understood by those skilled in the art that the following terms may include generic "R"-groups within their definitions, e.g., "the term alkoxy refers to an -OR substituent". It is also understood that within the definitions for the following terms, these "R" groups are included for illustration purposes and should not be construed as limiting or being limited by substitutions about Formula I.

[0007] The term "alkyl" refers to a branched, unbranched, or saturated cyclic carbon chain, including, but not limited to, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tertiary butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.

[0008] The term "alkenyl" refers to a branched, unbranched or cyclic carbon chain containing one or more double bonds including, but not limited to, ethenyl, propenyl, butenyl, isopropenyl, isobutenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, and the like.

[0009] The term "alkynyl" refers to a branched or unbranched carbon chain containing one or more triple bonds including, but not limited to, propynyl, butynyl, and the like.

[0010] The terms "aryl" and "Ar" refer to any aromatic ring, mono- or bi-cyclic, containing 0 heteroatoms. [0011] The term "heterocycle" refers to any aromatic or non-aromatic ring, mono- or tricyclic, containing one or more heteroatoms

[0012] The term "alkoxy" refers to an -OR substituent.

[0013] The term "acyloxy" refers to an -OC(0)R substituent.

[0014] The term "hydroxyl" refers to an -OH substituent.

[0015] The term "arylalkoxy" refers to -0(CH2) _n Ar where n is an integer selected from the list 1, 2, 3, 4, 5, or 6.

[0016] The term "haloalkoxy" refers to an -OR-X substituent, wherein X is CI, F, Br, or I, or any combination thereof.

[0017] The term "haloalkyl" refers to an alkyl, which is substituted with CI, F, I, or Br or any combination thereof.

[0018] The term "halogen" or "halo" refers to one or more halogen atoms, defined as F, CI, Br, and I.

[0019] The term thioalkyl refers to an -SR substituent.

[0020] Throughout the disclosure, reference to the compounds of Formula I is read as also including diastereomers, enantiomers, and mixtures thereof. In another embodiment, Formula (I) is read as also including salts or hydrates thereof. Exemplary salts include, but are not limited to: hydrochloride, hydrobromide, and hydroiodide.

[0021] It is also understood by those skilled in the art that additional substitution is allowable, unless otherwise noted, as long as the rules of chemical bonding and strain energy are satisfied and the product still exhibits fungicidal activity.

[0022] Another embodiment of the present disclosure is a use of a compound of Formula I, for protection of a plant against attack by a phytopathogenic organism or the treatment of a plant infested by a phytopathogenic organism, comprising the application of a compound of Formula I, or a composition comprising the compound to soil, a plant, a part of a plant, foliage, and/or roots.

[0023] Additionally, another embodiment of the present disclosure is a composition useful for protecting a plant against attack by a phytopathogenic organism and/or treatment of a plant infested by a phytopathogenic organism comprising a compound of Formula I and a phytologically acceptable carrier material. DETAILED DESCRIPTION

[0024] The compounds of the present disclosure may be applied by any of a variety of known techniques, either as the compounds or as formulations comprising the compounds. For example, the compounds may be applied to the roots or foliage of plants for the control of various fungi, without damaging the commercial value of the plants. The materials may be applied in the form of any of the generally used formulation types, for example, as solutions, dusts, wettable powders, flowable concentrate, or emulsifiable concentrates.

[0025] Preferably, the compounds of the present disclosure are applied in the form of a formulation, comprising one or more of the compounds of Formula I with a phytologically acceptable carrier. Concentrated formulations may be dispersed in water, or other liquids, for application, or formulations may be dust-like or granular, which may then be applied without further treatment. The formulations can be prepared according to procedures that are conventional in the agricultural chemical art.

[0026] The present disclosure contemplates all vehicles by which one or more of the compounds may be formulated for delivery and use as a fungicide. Typically, formulations are applied as aqueous suspensions or emulsions. Such suspensions or emulsions may be produced from water-soluble, water-suspendible, or emulsifiable formulations which are solids, usually known as wettable powders; or liquids, usually known as emulsifiable concentrates, aqueous suspensions, or suspension concentrates. As will be readily appreciated, any material to which these compounds may be added may be used, provided it yields the desired utility without significant interference with the activity of these compounds as antifungal agents.

[0027] Wettable powders, which may be compacted to form water-dispersible granules, comprise an intimate mixture of one or more of the compounds of Formula I, an inert carrier and surfactants. The concentration of the compound in the wettable powder may be from about 10 percent to about 90 percent by weight based on the total weight of the wettable powder, more preferably about 25 weight percent to about 75 weight percent. In the preparation of wettable powder formulations, the compounds may be compounded with any finely divided solid, such as prophyllite, talc, chalk, gypsum, Fuller's earth, bentonite, attapulgite, starch, casein, gluten, montmorillonite clays, diatomaceous earths, purified silicates or the like. In such operations, the finely divided carrier and surfactants are typically blended with the compound(s) and milled.

[0028] Emulsifiable concentrates of the compounds of Formula I may comprise a convenient concentration, such as from about 1 weight percent to about 50 weight percent of the compound, in a suitable liquid, based on the total weight of the concentrate. The compounds may be dissolved in an inert carrier, which is either a water-miscible solvent or a mixture of water-immiscible organic solvents, and emulsifiers. The concentrates may be diluted with water and oil to form spray mixtures in the form of oil-in-water emulsions. Useful organic solvents include aromatics, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, for example, terpenic solvents, including rosin derivatives, aliphatic ketones, such as cyclohexanone, and complex alcohols, such as 2- ethoxyethanol.

[0029] Emulsifiers which may be advantageously employed herein may be readily determined by those skilled in the art and include various nonionic, anionic, cationic and amphoteric emulsifiers, or a blend of two or more emulsifiers. Examples of nonionic emulsifiers useful in preparing the emulsifiable concentrates include the polyalkylene glycol ethers and condensation products of alkyl and aryl phenols, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propylene oxides such as the ethoxylated alkyl phenols and carboxylic esters solubilized with the polyol or polyoxyalkylene. Cationic emulsifiers include quaternary ammonium compounds and fatty amine salts. Anionic emulsifiers include the oil-soluble salts (e.g., calcium) of alkylaryl sulphonic acids, oil-soluble salts or sulfated polyglycol ethers and appropriate salts of phosphated polyglycol ether.

[0030] Representative organic liquids which may be employed in preparing the emulsifiable concentrates of the compounds of the present disclosure are the aromatic liquids such as xylene, propyl benzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkyl amides of various fatty acids, particularly the dimethyl amides of fatty glycols and glycol derivatives such as the n-butyl ether, ethyl ether or methyl ether of diethylene glycol, the methyl ether of Methylene glycol, petroleum fractions or hydrocarbons such as mineral oil, aromatic solvents, paraffinic oils, and the like; vegetable oils such as soy bean oil, rape seed oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cotton seed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; esters of the above vegetable oils; and the like. Mixtures of two or more organic liquids may also be employed in the preparation of the emulsifiable concentrate. Organic liquids include xylene, and propyl benzene fractions, with xylene being most preferred in some cases. Surface-active dispersing agents are typically employed in liquid formulations and in an amount of from 0.1 to 20 percent by weight based on the combined weight of the dispersing agent with one or more of the compounds. The formulations can also contain other compatible additives, for example, plant growth regulators and other biologically active compounds used in agriculture.

[0031] Aqueous suspensions comprise suspensions of one or more water-insoluble compounds of Formula I, dispersed in an aqueous vehicle at a concentration in the range from about 1 to about 50 weight percent, based on the total weight of the aqueous suspension. Suspensions are prepared by finely grinding one or more of the compounds, and vigorously mixing the ground material into a vehicle comprised of water and surfactants chosen from the same types discussed above. Other components, such as inorganic salts and synthetic or natural gums, may also be added to increase the density and viscosity of the aqueous vehicle.

[0032] The compounds of Formula I can also be applied as granular formulations, which are particularly useful for applications to the soil. Granular formulations generally contain from about 0.5 to about 10 weight percent, based on the total weight of the granular formulation of the compound(s), dispersed in an inert carrier which consists entirely or in large part of coarsely divided inert material such as attapulgite, bentonite, diatomite, clay or a similar inexpensive substance. Such formulations are usually prepared by dissolving the compounds in a suitable solvent and applying it to a granular carrier which has been preformed to the appropriate particle size, in the range of from about 0.5 to about 3 mm. A suitable solvent is a solvent in which the compound is substantially or completely soluble. Such formulations may also be prepared by making a dough or paste of the carrier and the compound and solvent, and crushing and drying to obtain the desired granular particle.

[0033] Dusts containing the compounds of Formula I may be prepared by intimately mixing one or more of the compounds in powdered form with a suitable dusty agricultural carrier, such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust. [0034] The formulations may additionally contain adjuvant surfactants to enhance deposition, wetting, and penetration of the compounds onto the target crop and organism. These adjuvant surfactants may optionally be employed as a component of the formulation or as a tank mix. The amount of adjuvant surfactant will typically vary from 0.01 to 1.0 percent by volume, based on a spray-volume of water, preferably 0.05 to 0.5 volume percent. Suitable adjuvant surfactants include, but are not limited to ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulphosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines, blends of surfactants with mineral or vegetable oils, crop oil concentrate (mineral oil (85%) + emulsifiers (15%)); nonylphenol ethoxylate; benzylcocoalkyldimethyl quaternary ammonium salt; blend of petroleum hydrocarbon, alkyl esters, organic acid, and anionic surfactant; C9 - Cn

alkylpolyglycoside; phosphated alcohol ethoxylate; natural primary alcohol (C12- C½) ethoxylate; di-sec-butylphenol EO-PO block copolymer; polysiloxane-methyl cap; nonylphenol ethoxylate + urea ammonium nitrrate; emulsified methylated seed oil; tridecyl alcohol (synthetic) ethoxylate (8EO); tallow amine ethoxylate (15 EO); PEG(400) dioleate-99. The formulations may also include oil-in-water emulsions such as those disclosed in U.S. Patent Application Serial No. 11/495,228, the disclosure of which is expressly incorporated by reference herein.

[0035] The formulations may optionally include combinations that contain other pesticidal compounds. Such additional pesticidal compounds may be fungicides, insecticides, herbicides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds. Accordingly, in such embodiments, the other pesticidal compound is employed as a supplemental toxicant for the same or for a different pesticidal use. The compounds of Formula I and the pesticidal compound in the combination can generally be present in a weight ratio of from 1:100 tol00:l.

[0036] The compounds of the present disclosure may also be combined with other fungicides to form fungicidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure are often applied in conjunction with one or more other fungicides to control a wider variety of undesirable diseases. When used in conjunction with other fungicide(s), the presently claimed compounds may be formulated with the other fungicide(s), tank-mixed with the other fungicide(s) or applied sequentially with the other fungicide(s). Such other fungicides may include 2-(thiocyanatomethylthio)-benzothiazole, 2-phenylphenol, 8-hydroxyquinoline sulfate, ametoctradin, amisulbrom, antimycin, Ampelomyces quisqualis, azaconazole, azoxystrobin, Bacillus subtilis, Bacillus subtilis strain QST713, benalaxyl, benomyl, benthiavalicarb-isopropyl, benzovindiflupyr benzylaminobenzene- sulfonate (BABS) salt, bicarbonates, biphenyl,

bismerthiazol, bitertanol, bixafen, blasticidin-S, borax, Bordeaux mixture, boscalid, bromuconazole, bupirimate, calcium polysulfide, captafol, captan, carbendazim, carboxin, carpropamid, carvone, chlazafenone, chloroneb, chlorothalonil, chlozolinate, Coniothyrium minitans, copper hydroxide, copper octanoate, copper oxychloride, copper sulfate, copper sulfate (tribasic), cuprous oxide, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dazomet, debacarb, diammonium ethylenebis-(dithiocarbamate), dichlofluanid, dichlorophen, diclocymet, diclomezine, dichloran, diethofencarb, difenoconazole, difenzoquat ion, diflumetorim, dimethomoφh, dimoxystrobin, diniconazole, diniconazole-M, dinobuton, dinocap, diphenylamine, dithianon, dodemorph, dodemorph acetate, dodine, dodine free base, edifenphos, enestrobin, enestroburin, epoxiconazole, ethaboxam, ethoxyquin, etridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumorph, fluopicolide, fluopyram, fluoroimide, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil, flutolanil, flutriafol, fluxapyroxad, folpet, formaldehyde, fosetyl, fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr, guazatine, guazatine acetates, GY-81, hexachlorobenzene, hexaconazole, hymexazol, imazalil, imazalil sulfate, imibenconazole, iminoctadine, iminoctadine triacetate, iminoctadine tris(albesilate), iodocarb, ipconazole, ipfenpyrazolone, iprobenfos, iprodione, iprovalicarb, isoprothiolane, isopyrazam, isotianil, kasugamycin, kasugamycin hydrochloride hydrate, kresoxim-methyl, laminarin, mancopper, mancozeb, mandipropamid, maneb, mefenoxam, mepanipyrim, mepronil, meptyl-dinocap, mercuric chloride, mercuric oxide, mercurous chloride, metalaxyl, metalaxyl-M, metam, metam-ammonium, metam-potassium, metam-sodium, metconazole, methasulfocarb, methyl iodide, methyl isothiocyanate, metiram, metominostrobin, metrafenone, mildiomycin, myclobutanil, nabam, nitrothal-isopropyl, nuarimol, octhilinone, ofurace, oleic acid (fatty acids), orysastrobin, oxadixyl, oxine-copper, oxpoconazole fumarate, oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen, pentachlorophenol,

pentachlorophenyl laurate, penthiopyrad, phenylmercury acetate, phosphonic acid, phthalide, picoxystrobin, polyoxin B, polyoxins, polyoxorim, potassium bicarbonate, potassium hydroxyquinoline sulfate, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, proquinazid, prothioconazole, pyraclostrobin,

pyrametostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, quinoclamine, quinoxyfen, quintozene, Reynoutria sachalinensis extract, sedaxane, silthiofam, simeconazole, sodium 2-phenylphenoxide, sodium bicarbonate, sodium pentachlorophenoxide, spiroxamine, sulfur, SYP-Z048, tar oils, tebuconazole, tebufloquin, tecnazene, tetraconazole, thiabendazole, thifluzamide, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazoxide, tricyclazole, tridemorph, trifloxystrobin, triflumizole, triforine, triticonazole, validamycin, valifenalate, valiphenal, vinclozolin, zineb, ziram, zoxamide, Candida oleophila, Fusarium oxysporum, Gliocladium spp., Phlebiopsis gigantea, Streptomyces griseoviridis, Trichoderma spp., ( ?S)-N-(3,5-dichlorophenyl)- 2-(methoxymethyl)-succinimide, 1,2-dichloropropane, l,3-dichloro-l,l,3,3-tetrafluoroacetone hydrate, 1 -chloro-2,4-dinitronaphthalene, 1 -chloro-2-nitropropane, 2-(2-heptadecyl-2-imidazolin- 1 - yl)ethanol, 2,3-dihydro-5-phenyl-l,4-dithi-ine 1,1,4,4-tetraoxide, 2-methoxyethylmercury acetate, 2-methoxyethylmercury chloride, 2-methoxyethylmercury silicate, 3-(4-chlorophenyl)-5- methylrhodanine, 4-(2-nitroprop-l-enyl)phenyl thiocyanateme, ampropylfos, anilazine, azithiram, barium polysulfide, Bayer 32394, benodanil, benquinox, bentaluron, benzamacril; benzamacril- isobutyl, benzamorf, binapacryl, bis(methylmercury) sulfate, bis(tributyltin) oxide, buthiobate, cadmium calcium copper zinc chromate sulfate, carbamorph, CECA, chlobenthiazone,

chloraniformethan, chlorfenazole, chlorquinox, climbazole, copper bis(3-phenylsalicylate), copper zinc chromate, cufraneb, cupric hydrazinium sulfate, cuprobam, cyclafuramid, cypendazole, cyprofuram, decafentin, dichlone, dichlozoline, diclobutrazol, dimethirimol, dinocton, dinosulfon, dinoterbon, dipyrithione, ditalimfos, dodicin, drazoxolon, EBP, ESBP, etaconazole, etem, ethirim, fenaminosulf, fenapanil, fenitropan, fluotrimazole, furcarbanil, furconazole, furconazole-cis, furmecyclox, furophanate, glyodine, griseofulvin, halacrinate, Hercules 3944, hexylthiofos, ICIA0858, isopamphos, isovaledione, mebenil, mecarbinzid, metazoxolon, methfuroxam, methylmercury dicyandiamide, metsulfovax, milneb, mucochloric anhydride, myclozolin, N-3,5- dichlorophenyl-succinimide, N-3-nitrophenylitaconimide, natamycin, N-ethylmercurio-4- toluenesulfonanilide, nickel bis(dimethyldithiocarbamate), OCH, phenylmercury dimethyldithiocarbamate, phenylmercury nitrate, phosdiphen, prothiocarb; prothiocarb hydrochloride, pyracarbolid, pyridinitril, pyroxychlor, pyroxyfur, quinacetol; quinacetol sulfate, quinazamid, quinconazole, rabenzazole, salicylanilide, SSF-109, sultropen, tecoram, thiadifluor, thicyofen, thiochlorfenphim, thiophanate, thioquinox, tioxymid, triamiphos, triarimol, triazbutil, trichlamide, urbacid, zarilamid, and any combinations thereof.

[0037] Additionally, the compounds described herein may be combined with other pesticides, including insecticides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure may be applied in conjunction with one or more other pesticides to control a wider variety of undesirable pests. When used in conjunction with other pesticides, the presently claimed compounds may be formulated with the other pesticide(s), tank-mixed with the other pesticide(s) or applied sequentially with the other pesticide(s). Typical insecticides include, but are not limited to: 1,2-dichloropropane, abamectin, acephate, acetamiprid, acethion, acetoprole, acrinathrin, acrylonitrile, alanycarb, aldicarb, aldoxycarb, aldrin, allethrin, allosamidin, allyxycarb, alpha-cypermethrin, alpha-ecdysone, alpha-endosulfan, amidithion, aminocarb, amiton, amiton oxalate, amitraz, anabasine, athidathion, azadirachtin, azamethiphos, azinphos-ethyl, azinphos-methyl, azothoate, barium hexafluorosilicate, barthrin, bendiocarb, benfuracarb, bensultap, beta-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bistrifluron, borax, boric acid, bromfenvinfos, bromocyclen, bromo-DDT, bromophos, bromophos-ethyl, bufencarb, buprofezin, butacarb, butathiofos, butocarboxim, butonate, butoxycarboxim, cadusafos, calcium arsenate, calcium polysulfide, camphechlor, carbanolate, carbaryl, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, cartap, cartap hydrochloride, chlorantraniliprole, chlorbicyclen, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorethoxyfos,

chlorfenapyr, chlorfenvinphos, chlorfluazuron, chlormephos, chloroform, chloropicrin,

chlorphoxim, chlorprazophos, chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, chromafenozide, cinerin I, cinerin Π, cinerins, cismethrin, cloethocarb, closantel, clothianidin, copper acetoarsenite, copper arsenate, copper naphthenate, copper oleate, coumaphos, coumithoate, crotamiton, crotoxyphos, crufomate, cryolite, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyclethrin, cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, cyphenothrin, cyromazine, cythioate, DDT, decarbofuran, deltamethrin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, demeton-S- methylsulphon, diafenthiuron, dialifos, diatomaceous earth, diazinon, dicapthon, dichlofenthion, dichlorvos, dicresyl, dicrotophos, dicyclanil, dieldrin, diflubenzuron, dilor, dimefluthrin, dimefox, dimetan, dimethoate, dimethrin, dimethylvinphos, dimetilan, dinex, dinex-diclexine, dinoprop, dinosam, dinotefuran, diofenolan, dioxabenzofos, dioxacarb, dioxathion, disulfoton, dithicrofos, d- limonene, DNOC, DNOC-ammonium, DNOC -potassium, DNOC-sodium, doramectin, ecdysterone, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothion, endrin, EPN, epofenonane, eprinomectin, esdepallethrine, esfenvalerate, etaphos, ethiofencarb, ethion, ethiprole, ethoate-methyl, ethoprophos, ethyl formate, ethyl-DDD, ethylene dibromide, ethylene dichloride, ethylene oxide, etofenprox, etrimfos, EXD, famphur, fenamiphos, fenazaflor, fenchlorphos, fenethacarb, fenfluthrin, fenitrothion, fenobucarb, fenoxacrim, fenoxycarb, fenpirithrin, fenpropathrin, fensulfothion, fenthion, fenthion-ethyl, fenvalerate, fipronil, flonicamid, flubendiamide, flucofuron, flucycloxuron, flucythrinate, flufenerim, flufenoxuron, flufenprox, fluvalinate, fonofos, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosmethilan, fospirate, fosthietan, furathiocarb, furethrin, gamma- cyhalothrin, gamma-HCH, halfenprox, halofenozide, HCH, HEOD, heptachlor, heptenophos, heterophos, hexaflumuron, HHDN, hydramethylnon, hydrogen cyanide, hydroprene, hyquincarb, imidacloprid, imiprothrin, indoxacarb, iodomethane, IPSP, isazofos, isobenzan, isocarbophos, isodrin, isofenphos, isofenphos-methyl, isoprocarb, isoprothiolane, isothioate, isoxathion, ivermectin, jasmolin I, jasmolin Π, jodfenphos, juvenile hormone I, juvenile hormone II, juvenile hormone ΠΙ, kelevan, kinoprene, lambda-cyhalothrin, lead arsenate, lepimectin, leptophos, lindane, lirimfos, lufenuron, lythidathion, malathion, malonoben, mazidox, mecarbam, mecarphon, menazon, mephosfolan, mercurous chloride, mesulfenfos, metaflumizone, methacrifos, methamidophos, methidathion, methiocarb, methocrotophos, methomyl, methoprene,

methoxychlor, methoxyfenozide, methyl bromide, methyl isothiocyanate, methylchloroform, methylene chloride, metofluthrin, metolcarb, metoxadiazone, mevinphos, mexacarbate, milbemectin, milbemycin oxime, mipafox, mirex, molosultap, monocrotophos, monomehypo, monosultap, morphothion, moxidectin, naftalofos, naled, naphthalene, nicotine, nilluridide, nitenpyram, nithiazine, nitrilacarb, novaluron, noviflumuron, omethoate, oxamyl, oxydemeton- methyl, oxydeprofos, oxydisulfoton, para-dichlorobenzene, parathion, parathion-methyl, penlluron, pentachlorophenol, permethrin, phenkapton, phenothrin, phenthoate, phorate, phosalone, phosfolan, phosmet, phosnichlor, phosphamidon, phosphine, phoxim, phoxim-methyl, pirimetaphos, pirimicarb, pirimiphos-ethyl, pirimiphos-methyl, potassium arsenite, potassium thiocyanate, pp'- DDT, prallethrin, precocene I, precocene Π, precocene ΠΙ, primidophos, profenofos, profluralin, promacyl, promecarb, propaphos, propetamphos, propoxur, prothidathion, prothiofos, prothoate, protrifenbute, pyraclofos, pyralluprole, pyrazophos, pyresmethrin, pyrethrin I, pyrethrin Π, pyrethrins, pyridaben, pyridalyl, pyridaphenthion, pyrifluquinazon, pyrimidifen, pyrimitate, pyriprole, pyriproxyfen, quassia, quinalphos, quinalphos-methyl, quinothion, rafoxanide, resmethrin, rotenone, ryania, sabadiUa, schradan, selamectin, silafluofen, silica gel, sodium arsenite, sodium fluoride, sodium hexafluorosilicate, sodium thiocyanate, sophamide, spinetoram, spinosad, spiromesifen, spirotetramat, sulcofuron, sulcofuron- sodium, sulfluramid, sulfotep, sulfoxaflor, sulfuryl fluoride, sulprofos, tau-fluvalinate, tazimcarb, TDE, tebufenozide, tebufenpyrad, tebupirimfos, teflubenzuron, tefluthrin, temephos, TEPP, terallethrin, terbufos, tetrachloroethane, tetrachlorvinphos, tetramethrin, tetramethylfluthrin, theta-cypermethrin, thiacloprid, thiamethoxam, thicrofos, thiocarboxime, thiocyclam, thiocyclam oxalate, thiodicarb, thiofanox, thiometon, thiosultap, thiosultap-disodium, thiosultap-monosodium, thuringiensin, tolfenpyrad, tralomethrin, transfluthrin, transpermethrin, triarathene, triazamate, triazophos, trichlorfon, trichlormetaphos-3, trichloronat, trifenofos, triflumuron, trimethacarb, triprene, vamidothion, vaniliprole, XMC, xylylcarb, zeta-cypermethrin, zolaprofos, and any combinations thereof.

[0038] Additionally, the compounds described herein may be combined with herbicides that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure may be applied in conjunction with one or more herbicides to control a wide variety of undesirable plants. When used in conjunction with herbicides, the presently claimed compounds may be formulated with the herbicide(s), tank-mixed with the herbicide(s) or applied sequentially with the herbicide(s). Typical herbicides include, but are not limited to: 4-CPA; 4-CPB; 4-CPP; 2,4-D; 3,4-DA; 2,4-DB; 3,4-DB; 2,4-DEB; 2,4-DEP; 3,4-DP; 2,3,6-TBA; 2,4,5-T; 2,4,5-TB; acetochlor, acifluorfen, aclonifen, acrolein, alachlor, allidochlor, alloxydim, allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone, amidosulfuron, aminocyclopyrachlor, aminopyralid, amiprofos-methyl, amitrole, ammonium sulfamate, anilofos, anisuron, asulam, atraton, atrazine, azafenidin, azimsulfuron, aziprotryne, barban, BCPC, beilubutamid, benazolin, bencarbazone, beniluralin, benfuresate, bensulfuron, bensulide, bentazone, benzadox, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzoylprop, benzthiazuron, bicyclopyrone, bifenox, bilanafos, bispyribac, borax, bromacil, bromobonil, bromobutide, bromofenoxim, bromoxynil, brompyrazon, butachlor, butafenacil, butamifos, butenachlor, buthidazole, buthiuron, butralin, butroxydim, buturon, butylate, cacodylic acid, cafenstrole, calcium chlorate, calcium cyanamide, cambendichlor, carbasulam, carbetamide, carboxazole chlorprocarb, carfentrazone, CDEA, CEPC, chlomethoxyfen,

chloramben, chloranocryl, chlorazifop, chlorazine, chlorbromuron, chlorbufam, chloreturon, chlorfenac, chlorfenprop, chlorflurazole, chlorflurenol, chloridazon, chlorimuron, chlornitrofen, chloropon, chlorotoluron, chloroxuron, chloroxynil, chlorpropham, chlorsulfuron, chlorthal, chlorthiamid, cinidon-ethyl, cinmethylin, cinosulfuron, cisanilide, clethodim, cliodinate, clodinafop, clofop, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, cloransulam, CMA, copper sulfate, CPMF, CPPC, credazine, cresol, cumyluron, cyanatryn, cyanazine, cycloate,

cyclosulfamuron, cycloxydim, cycluron, cyhalofop, cyperquat, cyprazine, cyprazole, cypromid, daimuron, dalapon, dazomet, delachlor, desmedipham, desmetryn, di-allate, dicamba, dichlobenil, dichloralurea, dichlormate, dichlorprop, dichlorprop-P, diclofop, diclosulam, diethamquat, diethatyl, difenopenten, difenoxuron, difenzoquat, diflufenican, diflufenzopyr, dimefuron, dimepiperate, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimexano, dimidazon, dinitramine, dinofenate, dinoprop, dinosam, dinoseb, dinoterb, diphenamid, dipropetryn, diquat, disul, dithiopyr, diuron, DMPA, DNOC, DSMA, EBEP, eglinazine, endothal, epronaz, EPTC, erbon, esprocarb, ethalfluralin, ethametsulfuron, ethidimuron, ethiolate, ethofumesate, ethoxyfen, ethoxysulfuron, etinofen, etnipromid, etobenzanid, EXD, fenasulam, fenoprop, fenoxaprop, fenoxaprop-P, fenoxasulfone, fenteracol, fenthiaprop, fentrazamide, fenuron, ferrous sulfate, flamprop, flamprop- M, flazasulfuron, florasulam, fluazifop, fluazifop-P, fluazolate, flucarbazone, flucetosulfuron, fluchloralin, flufenacet, flufenican, flufenpyr, flumetsulam, flumezin, flumiclorac, flumioxazin, flumipropyn, fluometuron, fluorodifen, fluoroglycofen, fluoromidine, fluoronitrofen, fluothiuron, ilupoxam, flupropacil, flupropanate, ilupyrsulfuron, iluridone, flurochloridone, iluroxypyr, flurtamone, fluthiacet, fomesafen, foramsulfuron, fosamine, furyloxyfen, glufosinate, glufosinate-P, glyphosate, halauxifen, halosafen, halosulfuron, haloxydine, haloxyfop, haloxyfop-P,

hexachloroacetone, hexaflurate, hexazinone, imazamethabenz, imazamox, imazapic, imazapyr, imazaquin, imazethapyr, imazosulfuron, indanofan, indaziflam, iodobonil, iodomethane, iodosulfuron, ioxynil, ipazine, ipfencarbazone, iprymidam, isocarbamid, isocil, isomethiozin, isonoruron, isopolinate, isopropalin, isoproturon, isouron, isoxaben, isoxachlortole, isoxaflutole, isoxapyrifop, karbutilate, ketospiradox, lactofen, lenacil, linuron, MAA, MAMA, MCPA, MCPA- thioethyl, MCPB, mecoprop, mecoprop-P, medinoterb, mefenacet, mefluidide, mesoprazine, mesosulfuron, mesotrione, metam, metamifop, metamitron, metazachlor, metazosulfuron, metflurazon, methabenzthiazuron, methalpropalin, methazole, methiobencarb, methiozolin, methiuron, methometon, methoprotryne, methyl bromide, methyl isothiocyanate, methyldymron, metobenzuron, metobromuron, metolachlor, metosulam, metoxuron, metribuzin, metsulfuron, molinate, monalide, monisouron, monochloroacetic acid, monolinuron, monuron, morfamquat, MSMA, naproanilide, napropamide, naptalam, neburon, nicosulfuron, nipyraclofen, nitralin, nitrofen, nitrofluorfen, norflurazon, noruron, OCH, orbencarb, o/t zo-dichlorobenzene,

orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxapyrazon, oxasulfuron, oxaziclomefone, oxyfluorfen, parafluron, paraquat, pebulate, pelargonic acid, pendimethalin, penoxsulam, pentachlorophenol, pentanochlor, pentoxazone, perfluidone, pethoxamid, phenisopham, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenylmercury acetate, picloram, picolinafen, pinoxaden, piperophos, potassium arsenite, potassium azide, potassium cyanate, pretilachlor, primisulfuron, procyazine, prodiamine, profluazol, profluralin, profoxydim, proglinazine, prometon, prometryn, propachlor, propanil, propaquizafop, propazine, propham, propisochlor, propoxycarbazone, propyrisulfuron, propyzamide, prosulfalin, prosulfocarb, prosulfuron, proxan, prynachlor, pydanon, pyraclonil, pyraflufen, pyrasulfotole, pyrazolynate, pyrazosulfuron, pyrazoxyfen, pyribenzoxim, pyributicarb, pyriclor, pyridafol, pyridate, pyriftalid, pyriminobac, pyrimisulfan, pyrithiobac, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quinoclamine, quinonamid, quizalofop, quizalofop-P, rhodethanil, rimsulfuron, saflufenacil, S- metolachlor, sebuthylazine, secbumeton, sethoxydim, siduron, simazine, simeton, simetryn, SMA, sodium arsenite, sodium azide, sodium chlorate, sulcotrione, sulfallate, sulfentrazone, sulfometuron, sulfosulfuron, sulfuric acid, sulglycapin, swep, TCA, tebutam, tebuthiuron, tefuryltrione, tembotrione, tepraloxydim, terbacil, terbucarb, terbuchlor, terbumeton, terbuthylazine, terbutryn, tetrafluron, thenylchlor, thiazafluron, thiazopyr, thidiazimin, thidiazuron, thiencarbazone-methyl, thifensulfuron, thiobencarb, tiocarbazil, tioclorim, topramezone, tralkoxydim, triafamone, tri-allate, triasulfuron, triaziflam, tribenuron, tricamba, triclopyr, tridiphane, trietazine, trifloxysulfuron, trifluralin, triflusulfuron, trifop, trifopsime, trihydroxytriazine, trimeturon, tripropindan, tritac, tritosulfuron, vernolate, and xylachlor.

[0039] Another embodiment of the present disclosure is a method for the control or prevention of fungal attack. This method comprises applying to the soil, plant, roots, foliage, or locus of the fungus, or to a locus in which the infestation is to be prevented (for example applying to cereal or grape plants), a fungicidally effective amount of one or more of the compounds of Formula I. The compounds are suitable for treatment of various plants at fungicidal levels, while exhibiting low phytotoxicity. The compounds may be useful both in a protectant and/or an eradicant fashion.

[0040] The compounds have been found to have significant fungicidal effect particularly for agricultural use. Many of the compounds are particularly effective for use with agricultural crops and horticultural plants.

[0041] It will be understood by those skilled in the art that the efficacy of the compound for the foregoing fungi establishes the general utility of the compounds as fungicides.

[0042] The compounds have broad ranges of activity against fungal pathogens. Exemplary pathogens may include, but are not limited to, causing agent of wheat leaf blotch {Mycosphaerella graminicola; anamorph: Zymoseptoria tritici), wheat brown rust (Puccinia triticina), wheat stripe rust {Puccinia striiformis), scab of apple (Venturia inaequalis), powdery mildew of grapevine {Uncinula necator), barley scald {Rhynchosporium secalis), blast of rice {Magnaporthe grisea), rust of soybean {Phakopsora pachyrhizi), glume blotch of wheat {Leptosphaeria nodorum), powdery mildew of wheat {Blumeria graminisf. sp.tritici), powdery mildew of barley {Blumeria graminisf. sp. hordei), powdery mildew of cucurbits {Erysiphe dehor acearum), anthracnose of cucurbits {Glomerella lagenarium), leaf spot of beet {Cercospora beticola), early blight of tomato {Alternaria solani), and spot blotch of barley {Cochliobolus sativus). The exact amount of the active material to be applied is dependent not only on the specific active material being applied, but also on the particular action desired, the fungal species to be controlled, and the stage of growth thereof, as well as the part of the plant or other product to be contacted with the compound. Thus, all the compounds, and formulations containing the same, may not be equally effective at similar concentrations or against the same fungal species.

[0043] The compounds are effective in use with plants in a disease-inhibiting and

phytologically acceptable amount. The term "disease-inhibiting and phytologically acceptable amount" refers to an amount of a compound that kills or inhibits the plant disease for which control is desired, but is not significantly toxic to the plant. This amount will generally be from about 0.1 to about 1000 ppm (parts per million), with 1 to 500 ppm being preferred. The exact concentration of compound required varies with the fungal disease to be controlled, the type of formulation employed, the method of application, the particular plant species, climate conditions, and the like. A suitable application rate is typically in the range from about 0.10 to about 4 pounds/acre (about 0.01 to 0.45 grams per square meter, g/m ² ).

[0044] Any range or desired value given herein may be extended or altered without losing the effects sought, as is apparent to the skilled person for an understanding of the teachings herein.

[0045] The compounds of Formula I may be made using well-known chemical procedures. Intermediates not specifically mentioned in this disclosure are either commercially available, may be made by routes disclosed in the chemical literature, or may be readily synthesized from commercial starting materials utilizing standard procedures.

GENERAL SCHEMES

[0046] The following schemes illustrate approaches to generating picolinamide compounds of Formula (I). The following descriptions and examples are provided for illustrative purposes and should not be construed as limiting in terms of substituents or substitution patterns.

[0047] Compounds of Formula 1.4, where Ri and R ₂ are as originally defined, can be prepared according to the methods outlined in Scheme 1, steps a - c. Compounds of Formula 1.1, where Ri is as originally defined, can be obtained by reaction of (S)-5-methylfuran-2(5H)-one (Formula 1.0; prepared as reported in Kobayashi et al. Tetrahedron 2003, 59, 9743 - 9758) with a Grignard reagent, such as RiMgX, where Ri is as originally defined and X is a halide, for example bromide or chloride, and copper (I) iodide (Cul) in a polar, aprotic solvent such as THF at cryogenic temperatures of about -78 °C, as shown in step a. Compounds of Formula 1.2, where Ri is as originally defined, can be obtained from compounds of Formula 1.1, where Ri is as originally defined, by treatment with a reducing agent such as LAH in a polar, aprotic solvent such as THF, at a reduced temperature of about 0 °C as depicted in step b. Compounds of Formula 1.4, where Ri is as originally defined and R ₂ is as originally defined, for example ie/t-butoxy or benzyloxy, can be obtained from compounds of Formula 1.2 by treating with a protected aziridine of Formula 1.3, wherein R ₂ is as originally defined, for example (S)-l-ieri-butyl 2-methyl aziridine- 1,2- dicarboxylate or (S)-l -benzyl 2-methyl aziridine- 1,2-dicarboxylate, followed by treatment with a Lewis acid such as BF ₃ Et2 in a halogenated solvent such as CH ₂ C1 ₂ at reduced temperatures from about 0 °C to ambient temperature, as is depicted in step c.

Scheme 1

1.2 1 .3

[0048] Compounds of Formula 2.1, wherein Ri and R ₂ are as originally defined, can be prepared according to the methods outlined in Scheme 2, steps a - b. Compounds of Formula 2.0, wherein Ri and R ₂ are as originally defined, can be prepared from compounds of Formula 1.4, by treating with a hydroxide base, such as lithium hydroxide (LiOH), in an aqueous solvent system, such as THF/water, at about 22 °C, as depicted in step a. Compounds of formula 2.1, wherein Ri and R ₂ are as originally defined, can be prepared by adding a solution of the compound of Formula 2.0 in a halogenated solvent such as CH ₂ C1 ₂ or an aromatic solvent such as PhCH ₃ to a mixture of a base, such as DMAP, and a mixed anhydride, such as 2-methyl-6-nitrobenzoic anhydride (MNBA), in either a halogenated solvent such as CH ₂ C1 ₂ or an aromatic solvent such as PhCH ₃ at a temperature between about 21 °C and about 60 °C over a period of 4 - 12 hours (h), as shown in step b.

Scheme 2

2.0 2.1

[0049] Compounds of of Formula 3.2, wherein Ri is as originally defined, can be prepared through the methods shown in Scheme 3, steps a - c. Compounds of Formula 3.0, wherein Ri is as orginally defined, can be obtained from compounds of Formula 2.1, wherein Ri is as orginally defined and R ₂ is ie/t-butoxy, by treating with an acid, such as a solution of 4.0 Molar (M) hydrogen chloride (HC1) in dioxane, in an an aprotic solvent like CH ₂ C1 ₂ at about 22 °C, as shown in step a. Compounds of Formula 3.1, wherein Ri is as orginally defined, can be prepared from compounds of Formula 2.1, wherein Ri is as orginally defined and R ₂ is benzyloxy, by treating with H ₂ in the presence of a palladium catalyst, for example palladium on carbon (Pd/C, 5 or 10 weight %), in a polar solvent like ethyl acetate (EtOAc) at about 22 °C, as shown in step b. Compounds of Formula 3.2, wherein Ri is as originally defined, can be prepared from compounds of Formula 3.0 or Fomula 3.1, by treating with 3-hydroxy-4-methoxypicolinic acid in the presence of a base, such as N^V-diisopropylethylamine (DIPEA), and a peptide coupling reagent, such as benzotriazol-l-yl- oxytripyrrolidino-phosphonium hexafluorophosphate (PyBOP), in an aprotic solvent such as CH ₂ C1 ₂ , as shown in step c. Scheme 3

3.2

[0050] Compounds of of Formula 4.0, where Ri and R ₃ are as originally defined, can be prepared by the method shown in Scheme 4. Compounds of Formula 4.0, where Ri and R ₃ are as originally defined, can be prepared from compounds of Formula 3.2, where Ri is as originally defined, by treatment with the appropriate alkyl halide with or without a reagent such as sodium iodide (Nal) and an alkali carbonate base such as sodium carbonate (Na2C0 ₃ ) or potassium carbonate (K2C0 ₃ ) in a solvent such as acetone, or by treatment with an acyl halide in the presence of an amine base, such as pyridine, Et ₃ N, DMAP, or mixtures thereof in an aprotic solvent such as DCM, as shown in step a. Scheme 4

3.2 4.0

EXAMPLES

[0051] Example 1, Step 1: Preparation of (4tf,5S)-4-benzyl-5-methyldihydrofuran-2(3H)- one:

[0052] To a suspension of copper(I) iodide (7.76 grams (g), 40.8 millimoles (mmol)) in 50 milliliters (mL) of diethyl ether (Et ₂ 0) at -78 °C was added benzylmagnesium chloride (2.0 Molar (M) in tetrahydrofuran (THF), 40.8 mL, 82.0 mmol) dropwise. After stirring between -30 and -20 °C for 1 hour (h), the reaction mixture became a homogenous, dark brown solution. The solution was cooled to -78 °C and (S)-5-methylfuran-2(5H)-one (3.40 g, 29.1 mmol) in Et ₂ 0 (8 mL) was added slowly. The reaction was stirred at -78 °C for 2 hours (h), at which time thin layer

chromatography (TLC) analysis showed the reaction to be complete. The reaction was quenched with saturated aqueous ammonium chloride (NH ₄ C1) and filtered through Celite ^® to remove the inorganic salts. The filtrate was extracted with Et ₂ 0 (3x), and the combined organic extracts were dried over sodium sulfate (Na ₂ S0 ₄ ), filtered, concentrated, and purified by flash chromatography (silica gel (Si0 ₂ ), 0-^30% ethyl acetate (EtOAc) in hexanes) to provide the title compound (2.16 g, 39%) as a colorless oil: ¾ NMR (400 MHz, CDCI3) δ 7.37 - 7.12 (m, 5H), 4.43 - 4.26 (m, 1H),

2.83 (dd, / = 13.7, 6.4 Hz, 1H), 2.70 (dd, / = 13.8, 8.1 Hz, 1H), 2.61 (dd, / = 16.8, 7.6 Hz, 1H), 2.46 - 2.36 (m, 1H), 2.32 (dd, J = 16.8, 8.9 Hz, 1H), 1.31 (d, J = 6.2 Hz, 3H); ¹³ C NMR (101 MHz, CDCb) δ 176.01, 138.47, 128.75, 126.73, 81.48, 44.57, 38.46, 35.04, 19.87; GC-MS: 190.0.

[0053] Example 1, Step 2: Preparation of (3 ?,4S)-3-benzylpentane-l,4-diol:

[0054] To a solution of (4tf ,5S)-4-benzyl-5-methyldihydrofuran-2(3H)-one (650 mg, 3.42 mmol) in 17 mL THF at 0 °C was added lithium aluminum hydride (LAH, 1.0 M in THF, 4.10 mL, 4.10 mmol). The reaction mixture was slowly warmed to room temperature overnight, and carefully quenched at 0 °C with dropwise addition of 0.2 mL water, followed by 0.8 mL IN NaOH. To the mixture was added anhydrous Na ₂ S0 ₄ , filtered, concentrated, and purified by flash chromatography (silica gel (S1O2), 0-^70% ethyl acetate (EtOAc) in hexanes) to provide the title compound (580 mg, 87%) as a colorless oil: ^l H NMR (400 MHz, CDCb) δ 7.34 - 7.15 (m, 5H), 3.81 (qd, J = 6.4, 4.5 Hz, 1H), 3.73 (ddd, J = 10.8, 7.8, 4.6 Hz, 1H), 3.58 (ddd, J = 11.1, 6.5, 4.8 Hz, 1H), 2.85 (dd, = 13.6, 6.6 Hz, 1H), 2.54 (dd, 7 = 13.6, 8.4 Hz, 1H), 2.39 (s, 2H), 1.92 - 1.82 (m, 1H), 1.76 (ddt, J = 14.8, 7.8, 4.8 Hz, 1H), 1.66 - 1.56 (m, 1H), 1.25 (d, J = 6.4 Hz, 3H); ¹³ C NMR (101 MHz, CDCb) δ 140.79, 129.12, 128.41, 125.98, 69.10, 60.27, 44.83, 36.99, 31.59, 21.24; EIMS mJz 389 ([M+H] ⁺ ).

[0055] Example 1, Step 3: Preparation of (S)-methyl -3-(((3R,45 -3-benzyl-4- hydroxypentyl)oxy)-2-(((benzyloxy)carbonyl)amino)propanoate:

[0056] To a solution of (S)-l -benzyl 2-methyl aziridine-l,2-dicarboxylate (460 mg, 1.96 mmol) and (3R,45)-3-benzylpentane-l,4-diol (570 mg, 2.93 mmol) in 39 mL DCM at 0 °C was added BF3*0(Et) ₂ (48.3 μΐ, 0.391 mmol). The reaction was slowly warmed to room temperature overnight. The reaction mixture was quenched by the addition of saturated aqueous NaHC0 ₃ , and extracted with EtOAc (3x). The combined organic phases were concentrated and purified by column chromatography (silica gel (Si0 ₂ ), 0-^20% ethyl acetate (EtOAc) in DCM) to provide the title compound (430 mg, 51%) as a colorless oil: ¾ NMR (400 MHz, CDC1 ) δ 7.42 - 7.22 (m, 6H), 7.22 - 7.10 (m, 4H), 5.64 (d, / = 8.3 Hz, 1H), 5.13 (s, 2H), 4.62 - 4.44 (m, 1H), 3.87 - 3.69 (m, 2H), 3.75 (s, 3H), 3.68 - 3.55 (m, 1H), 3.49 (dt, J = 9.4, 5.9 Hz, 1H), 3.37 (ddt, J = 15.6, 9.5, 4.9 Hz, 1H), 2.78 (dd, / = 13.7, 6.4 Hz, 1H), 2.46 (dd, / = 13.6, 8.6 Hz, 1H), 1.82 - 1.72 (m, 1H), 1.65 - 1.54 (m, 2H), 1.17 (d, = 6.4 Hz, 3H); ESIMS mJz 430 ([M+H] ⁺ ).

[0057] Example 2, Step 1 : Preparation of (S)-3-(((3tf ,4S)-3-benzyl-4-hydroxypentyl)oxy)-2- (((benzyloxy)carbonyl)amino)propanoic acid:

[0058] To a solution of (S)-methyl -3-(((3tf ,4S)-3-benzyl-4-hydroxypentyl)oxy)-2- (((benzyloxy)carbonyl)amino)propanoate (640 mg, 1.49 mmol) in 10 mL THF and 5 mL water at room temperature was added LiOH ^» H ₂ 0 (375 mg, 8.94 mmol). The reaction was stirred at room temperature for 2 h, quenched with 1 N HC1, the phases separated, and the aqueous phase extracted with additional EtOAc (3x). The combined organic phases were washed with saturated aqueous NaHC0 ₃ , dried over Na ₂ S0 ₄ , filtered, and concentrated to furnish the title compound (600 mg, 97%) as a colorless oil: ESIMS m/z 416 ([M+H] ⁺ ).

[0059] Example 2, Step 2: Preparation of benzyl ((3S, 8tf ,9S)-8-benzyl-9-methyl-2-oxo- 1 ,5- dioxonan-3-yl)carbamate:

[0060] A solution of (S)-3-(((3tf ,4S)-3-benzyl-4-hydroxypentyl)oxy)-2- (((benzyloxy)carbonyl)amino)propanoic acid (600 mg, 1.44 mmol) in 30 mL DCM was added over a 3 h period via a syringe pump to a solution of MNBA (1.03 g, 2.98 mmol) and DMAP (1.09 g, 8.94 mmol) in 180 mL DCM at rt. The reaction mixture was stirred at rt overnight, concentrated, and the residue was purified by flash chromatography (S1O2, 0~ 10% EtOAc in hexanes) to provide the title compound (204 mg, 34%) as a colorless oil: See Table 2 for characterization data.

[0061] Example 3, Step 1 : Preparation of (3S, 8tf ,9S)-8-ethyl-9-methyl-2-oxo- 1 ,5-dioxonan- 3-aminium chloride:

[0062] To a solution of te/t-butyl (3S, 8tf ,9S)-8-ethyl-9-methyl-2-oxo-l,5-dioxonan-3- yl)carbamate (144 mg, 0.478 mmol) in 2.4 mL DCM at rt was added HC1 (4 M in dioxane, 1.20 mL, 4.78 mmol) and the reaction mixture was stirred at rt for 3 h. The solvent was evaporated in vacuo to provide the title compound (114 mg, 100%) as a colorless oil: See Table 2 for

characterization data.

[0063] Example 3, Step 2: Preparation of (3S, 8 ?,9S)-8-ethyl-9-methyl-2-oxo-l,5-dioxonan- 3-aminium chloride:

[0064] To a solution of benzyl ((35, 8R,95 -8-benzyl-9-methyl-2-oxo-l,5-dioxonan-3- yl)carbamate (204 mg, 0.513 mmol) in 10 mL EtOAc was added 5% Pd/C (54.6 mg, 0.0256 mmol) and the reaction was hydrogenated in a steel reactor under 500 psi of H ₂ at rt for 20 h. The reaction mixture was filtered through a pad of Celite ^® , concentrated and dried under high vacuum to yield the title compound (135 mg, 100% yield) as a white solid: See Table 2 for characterization data.

[0065] Example 3, Step 3: Preparation of N-((3S, 8R.95 - 8-benzyl-9-methyl-2-oxo-l,5- dioxonan-3-yl)-3-hydroxy-4-methoxypicolinamide:

[0066] To a solution of (3S, 8 ?,9S)-8-ethyl-9-methyl-2-oxo-l,5-dioxonan-3-aminium chloride (135 mg, 0.513 mmol) in 5 mL DCM were added 3-hydroxy-4-methoxypicolinic acid (95 mg, 0.564 mmol) and PyBOP (293 mg, 0.564 mmol). To the resulting suspension was added N- ethyl-N-isopropylpropan-2-amine (295 μί, 1.69 mmol) and after 1 h, the reaction was concentrated and the residue was purified by flash chromatography (Si0 ₂ , 0-^50% acetone in hexanes) to provide the title compound (183 mg, 86%) as a colorless foam: See Table 2 for characterization data.

[0067] Example 4: Preparation of ((2-(((3S, 8tf ,9S)-8-benzyl-9-methyl-2-oxo- 1 ,5-dioxonan- 3-yl)carbamoyl)-4-methoxypyridin-3-yl)oxy)methyl acetate:

[0068] To a solution of N-((3S, SR,9S)- 8-benzyl-9-methyl-2-oxo-l,5-dioxonan-3-yl)-3- hydroxy-4-methoxypicolinamide (82 mg, 0.198 mmol) in 4 mL acetone were added bromomethyl acetate (29.1 μί, 0.297 mmol) and K2CO3 (54.7 mg, 0.396 mmol), and the solution was heated to 50 °C and stirred for 2 h. The solution was cooled to rt and concentrated, and the residue was purified by flash chromatography (S1O2, 0"M00% EtOAc in hexanes) to provide the title compound (72 mg, 75%) as a colorless oil: See Table 2 for characterization data.

[0069] Example 5: Preparation of 2-(((3S, 8tf ,9S)-8-benzyl-9-methyl-2-oxo- 1 ,5-dioxonan-3- yl)carbamoyl)-4-methoxypyridin-3-yl) acetate:

[0070] To a solution of N-((3S, SR,9S)- 8-benzyl-9-methyl-2-oxo-l,5-dioxonan-3-yl)-3- hydroxy-4-methoxypicolinamide (74 mg, 0.179 mmol), Et ₃ N (49.8 μί, 0.357 mmol) and DMAP (4.4 mg, 0.036 mmol) in 3.6 mL DCM was added acetyl chloride (19 μί, 0.268 mmol) at rt, and the reaction color gradually turned to orange. After stirring at rt for 2 h, the reaction mixture was purified by flash chromatography (S1O2, 5-^50% acetone in hexanes) to provide the title compound (78 mg, 96%) as a colorless oil: See Table 2 for characterization data.

[0071] Example A: Evaluation of Fungicidal Activity: Leaf Blotch of Wheat (Mycosphaerella graminicola; Anamorph: Zymoseptoria tritici; Bayer code SEPTTR):

[0072] Technical grades of materials were dissolved in acetone, which were then mixed with nine volumes of water containing 110 ppm Triton X-100. The fungicide solutions were applied onto wheat seedlings using an automated booth sprayer to run-off. All sprayed plants were allowed to air dry prior to further handling. All fungicides were evaluated using the aforementioned method for their activity vs. all target diseases, unless stated otherwise. Wheat leaf blotch and brown rust activity were also evaluated using track spray applications, in which case the fungicides were formulated as EC formulations, containing 0.1% Trycol 5941 in the spray solutions.

[0073] Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Septoria tritici either prior to or after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two to three days in a lighted dew chamber at 20 °C) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20 °C for disease to develop. When disease symptoms were fully expressed on the 1 ^st leaves of untreated plants, infection levels were assessed on a scale of 0 to 100 percent disease severity. Percent disease control was calculated using the ratio of disease severity on treated plants relative to untreated plants.

[0074] Example B: Evaluation of Fungicidal Activity: Wheat Brown Rust {Puccinia triticina; Synonym: Puccinia reconditaf. sp. tritici; Bayer code PUCCRT):

[0075] Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Puccinia triticina either prior to or after fungicide treatments. After inoculation the plants were kept in a dark dew room at 22 °C with 100% relative humidity overnight to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 24 °C for disease to develop. Fungicide formulation, application and disease assessment followed the procedures as described in the Example A.

[0076] Example C: Evaluation of Fungicidal Activity: Asian Soybean Rust (Phakopsora pachyrhizi; Bayer code PHAKPA):

[0077] Technical grades of materials were dissolved in acetone, which were then mixed with nine volumes of water containing 0.011% Tween 20. The fungicide solutions were applied onto soybean seedlings using an automated booth sprayer to run-off. All sprayed plants were allowed to air dry prior to further handling.

[0078] Soybean plants (variety Williams 82) were grown in soil-less Metro mix, with one plant per pot. Two weeks old seedlings were used for testing. Plants were inoculated either 3 days prior to or 1 day after fungicide treatments. Plants were incubated for 24 h in a dark dew room at 22 °C and 100 % relative humidity then transferred to a growth room at 23 °C for disease to develop. Disease severity was assessed on the sprayed leaves.

Table 1. Compound Structure and Appearance

Cmpd. No. - Compound Number

Table 2. Analytical Data

*Cmpd. NMR

IR (cm ¹ ) MASS

No. (1H ¹³ C or ¹⁹ F) lH NMR (400 MHz, CD ₃ OD) δ 7.40 - 7.08 (m, 5H), 5.13 (dq, = 9.1, 6.3 Hz, 1H), 5.05 (s, 2H), 4.38 (t, = 3.5 Hz, 1H), 4.14 - 3.93 (m, 3H), 3.39 - 3.22 (m, 1H), 2.84 (dd, = 13.7, 4.5 Hz, 1H), 2.33 (dd, = 13.7, 9.7 Hz, 1H), 2.12 -

ESIMS m/z 264 1.93 (m, 1H), 1.78 (ddt, = 16.5, 8.4, 1.9

3

([Μ+ΗΓ) Hz, 1H), 1.45 (d, = 6.3 Hz, 3H), 1.40 - 1.26 (m, 1H).

¹³ C NMR (101 MHz, CD3ODCD3OD) δ 169.51, 140.99, 130.38, 129.59, 127.38, 78.55, 77.57, 72.90, 56.20, 50.15, 39.17,

34.12, 20.24.

ESIMS mJz 278.3

4

([M+H] ⁺ )

ESIMS mJz 306.3

5

([M+H] ⁺ ) lH NMR (400 MHz, CDCI3CDCI3) δ 6.82 (s, 2H), 5.11 - 4.94 (m, 1H), 4.32 (s,

ESIMS mJz 244.3 1H), 4.26 - 3.96 (m, 3H), 3.43 - 3.26 (m,

6

([M+H] ⁺ ) 1H), 1.70 - 1.39 (m, 3H), 1.40 - 1.23 (m,

1H), 1.34 (d, = 6.2 Hz, 3H), 1.23 - 1.06 (m, 4H), 0.91 - 0.82 (m, 6H). lH NMR (400 MHz, CDCI3CDCI3) δ 6.12 (s, 2H), 4.93 (dt, = 12.0, 6.1 Hz, 1H), 4.23 (s, 1H), 4.07 (d, = 13.0 Hz,

ESIMS mJz 230.3 3H), 3.41 (q, = 11.9, 10.3 Hz, 1H),

7

([M+H] ⁺ ) 1.76 - 1.54 (m, 3H), 1.53 - 1.29 (m, 1H),

1.33 (d, = 6.1 Hz, 3H), 1.11 - 0.96 (m, 2H), 0.90 (d, = 6.6 Hz, 3H), 0.85 (d,

= 6.5 Hz, 3H). *Cmpd. NMR

IR (cm ¹ ) MASS

No. (1H ¹³ C or ¹⁹ F)

ESIMS m/z 202

8

([Μ+ΗΓ) lH NMR (400 MHz, CDCb) δ 12.05 (s, 1H), 8.76 (d, 7 = 8.1 Hz, 1H), 7.98 (d, 7 = 5.2 Hz, 1H), 7.38 - 7.06 (m, 5H), 6.86 (d, 7 = 5.2 Hz, 1H), 5.12 (dq, 7 = 9.2, 6.3 Hz, 1H), 4.98 (ddd, 7 = 8.1, 5.5, 4.0 Hz, 1H), 4.02 (dd, 7 = 11.5, 5.5 Hz, 1H), 3.95 - 3.90 (m, 1H), 3.92 (s, 3H), 3.85 (dd, 7 = 11.5, 4.0 Hz, 1H), 3.29 (ddd, 7 =

HRMS-FAB (m/z)

12.3, 8.2, 1.9 Hz, 1H), 2.85 (dd, 7 = 13.7, ([M+HD calcd for

9 4.2 Hz, 1H), 2.28 (dd, 7 = 13.8, 10.3 Hz,

1H), 2.03 - 1.91 (m, 1H), 1.68 (ddt, 7 = found, 415.1873.

16.3, 7.2, 2.0 Hz, 1H), 1.46 (d, 7 = 6.3 Hz, 3H), 1.44 - 1.32 (m, 1H).

¹³ C NMR (101 MHz, CDCb) δ 170.36, 168.94, 155.25, 148.66, 140.64, 139.51, 130.32, 129.14, 128.50, 126.28, 109.54, 76.45, 75.57, 74.01, 56.06, 53.58, 48.58,

38.37, 32.76, 19.92.

*H NMR (400 MHz, CDCI3CDCI3) δ 12.03 (d, 7 = 0.7 Hz, 1H), 8.75 (d, 7 = 8.0 Hz, 1H), 8.00 (d, 7 = 5.2 Hz, 1H),

IR (thin 7.34 - 7.25 (m, 2H), 7.23 - 7.11 (m, 3H), film) 6.86 (d, 7 = 5.2 Hz, 1H), 5.11 (dq, 7 = 3370.53, HRMS-ESI (m/z) 8.2, 5.8, 5.3 Hz, 1H), 4.96 (ddd, 7 = 8.1, 2937.90, ([M+HD calcd for 5.5, 4.2 Hz, 1H), 4.15 - 4.07 (m, 1H),

10

1742.46, C23H29N2O6, 429.202; 4.05 (dd, 7 = 11.5, 5.5 Hz, 1H), 3.94 (s, 1648.43, found, 429.2024 3H), 3.87 (dd, 7 = 11.6, 4.3 Hz, 1H), 1526.39, 3.51 - 3.42 (m, 1H), 2.70 (ddd, 7 = 13.8, 1241.92 10.3, 5.2 Hz, 1H), 2.55 (ddd, 7 = 13.8,

10.2, 6.2 Hz, 1H), 1.88 - 1.77 (m, 1H),

1.76 - 1.63 (m, 2H), 1.62 - 1.51 (m, 2H), 1.35 (d, 7 = 6.3 Hz, 3H). ^* Cmpd. NMR

IR (cm ¹ ) MASS

No. (1H ¹³ C or ¹⁹ F)

*H NMR (400 MHz, CDCI3) δ 12.01 (d,

IR (thin = 0.6 Hz, 1H), 8.67 (d, = 8.1 Hz, film) 1H), 7.98 (d, = 5.2 Hz, 1H), 7.38 - 3371.60, HRMS-ESI (m/z) 7.25 (m, 4H), 7.23 - 7.13 (m, 1H), 6.85 2961.72, ([M calcd for (d, = 5.2 Hz, 1H), 4.96 - 4.80 (m, 2H),

11 +HD

1742.70, C25H33N2O6, 457.2333; 3.97 (dd, = 11.6, 5.4 Hz, 1H), 3.93 (s, 1648.91, found, 457.2335 3H), 3.68 (dd, = 11.6, 4.9 Hz, 1H), 1526.66, 3.65 - 3.58 (m, 1H), 3.15 - 3.04 (m, 1H), 1242.41 1.65 - 1.45 (m, 5H), 1.36 (s, 3H), 1.35 (s,

3H), 1.17 (d, = 6.3 Hz, 3H). lH NMR (400 MHz, CDCI3) δ 12.04 (s, 1H), 8.75 (d, = 8.1 Hz, 1H), 8.00 (d,

IR (thin

= 5.3 Hz, 1H), 6.87 (d, = 5.2 Hz, 1H), film)

5.06 (dq, = 9.8, 6.3 Hz, 1H), 4.96 (ddd, 3373.23, HRMS-ESI (m/z)

= 8.0, 5.4, 4.3 Hz, 1H), 4.12 - 4.00 (m, 2951.36, ([M

12 +HD calcd for

2H), 3.94 (s, 3H), 3.86 (dd, = 11.6, 4.4 1743.60, C20H31N2O6, 395.2177;

Hz, 1H), 3.46 - 3.39 (m, 1H), 1.72 - 1.58 1649.17, found, 395.2178

(m, 2H), 1.57 - 1.44 (m, 2H), 1.42 - 1.30 1481.10,

(m, 1H), 1.36 (d, = 6.3 Hz, 3H), 1.27 - 1242.79

1.12 (m, 3H), 0.89 (d, = 6.6 Hz, 3H), 0.87 (d, = 6.6 Hz, 3H).

^X H NMR (400 MHz, CDCI3) δ 12.04 (d,

IR (thin = 0.6 Hz, 1H), 8.75 (d, = 8.1 Hz, film) 1H), 8.00 (d, = 5.1 Hz, 1H), 6.87 (d, 3369.23, HRMS-ESI (m/z) = 5.3 Hz, 1H), 5.04 - 4.92 (m, 2H), 4.11 2953.44, ([M+HD calcd for - 4.02 (m, 2H), 3.94 (s, 3H), 3.85 (dd,

13

1742.10, C19H29N2O6, 381.202; = 11.6, 4.4 Hz, 1H), 3.52 - 3.39 (m, 1H), 1648.36, found, 381.202 1.77 - 1.54 (m, 3H), 1.49 - 1.38 (m, 1H), 1437.76, 1.36 (d, = 6.2 Hz, 3H), 1.09 (dd, = 1242.27 7.5, 6.1 Hz, 2H), 0.92 (d, = 6.6 Hz,

3H), 0.87 (d, = 6.5 Hz, 3H).

*Cmpd. NMR

IR (cm ¹ ) MASS

No. (1H ¹³ C or ¹⁹ F) lH NMR (400 MHz, CDCb) δ 12.05 (d, = 0.7 Hz, 1H), 8.76 (d, = 8.1 Hz, 1H), 7.99 (d, = 5.2 Hz, 1H), 6.87 (d, = 5.2 Hz, 1H), 5.07 (dq, = 9.5, 6.3 Hz, 1H), 4.96 (ddd, 7 = 8.1, 5.5, 4.2 Hz, 1H),

4.15 - 4.01 (m, 2H), 3.94 (s, 3H), 3.87

HRMS-ESI (m/z)

(dd, = 11.5, 4.3 Hz, 1H), 3.45 (ddd, 7 = ([M+H] ⁺ ) calcd for

14 12.0, 8.3, 1.8 Hz, 1H), 1.74 - 1.40 (m,

4H), 1.36 (d, J = 6.3 Hz, 3H), 1.32 - 1.20 found, 353.1713

(m, 1H), 0.90 (t, J = 7.4 Hz, 3H).

¹³ C NMR (101 MHz, CDCb) δ 170.45, 168.90, 155.23, 148.63, 140.59, 130.33,

109.49, 76.52, 76.10, 74.16, 56.03, 53.53, 48.16, 33.62, 25.10, 19.49, 10.36.

*H NMR (400 MHz, CDCb) δ 8.78 (d, J = 8.4 Hz, 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.36 - 7.09 (m, 5H), 7.00 (d, J = 5.5 Hz, 1H), 5.09 (dq, J = 9.3, 6.3 Hz, 1H), 4.98 (ddd, J = 8.1, 5.6, 4.0 Hz, 1H), 3.98 (dd,

J = 11.5, 5.6 Hz, 1H), 3.94 - 3.90 (m, 1H), 3.89 (s, 3H), 3.80 (dd, J = 11.5, 4.1 Hz, 1H), 3.28 (ddd, J = 12.2, 8.2, 1.8 Hz,

HRMS-FAB (m/z)

1H), 2.85 (dd, J = 13.7, 4.1 Hz, 1H), ([M+HD calcd for

15 2.39 (s, 3H), 2.27 (dd, J = 13.8, 10.4 Hz,

1H), 2.04 - 1.90 (m, 1H), 1.66 (ddt, J = found, 415.1870.

16.1, 7.1, 1.9 Hz, 1H), 1.45 (d, J = 6.3 Hz, 3H), 1.43 - 1.34 (m, 1H).

¹³ C NMR (101 MHz, CDCb) δ 170.86, 168.85, 162.74, 159.38, 146.79, 141.34, 139.60, 137.47, 129.15, 128.50, 126.26,

109.85, 76.26, 75.43, 74.38, 56.29, 53.65, 48.54, 38.41, 32.92, 20.74, 19.94. *Cmpd. NMR

IR (cm ¹ ) MASS

No. (1H ¹³ C or ¹⁹ F) lH NMR (400 MHz, CDC1 ₃ ) δ 8.62 (d, 7 = 7.8 Hz, 1H), 8.28 (d, 7 = 5.4 Hz, 1H), 7.35 - 7.10 (m, 5H), 6.95 (d, 7 = 5.4 Hz, 1H), 5.74 (d, 7 = 0.9 Hz, 2H), 5.10 (dq, 7 = 9.3, 6.3 Hz, 1H), 5.01 (ddd, 7 = 7.8, 5.5, 4.0 Hz, 1H), 4.01 (dd, 7 = 11.5, 5.6 Hz, 1H), 3.95 - 3.91 (m, 1H), 3.90 (s, 3H), 3.84 (dd, 7 = 11.5, 4.0 Hz, 1H), 3.30 (ddd, 7 = 12.1, 8.1, 1.8 Hz, 1H),

HRMS-FAB im/z)

2.86 (dd, 7 = 13.7, 4.1 Hz, 1H), 2.28 (dd, ([M+HD calcd for

16 7 = 13.8, 10.4 Hz, 1H), 2.07 (s, 3H), 2.04

CisHsiNiOs, 487.2080;

- 1.95 (m, 1H), 1.67 (ddt, 7 = 16.1, 7.1, found, 487.2086.

1.9 Hz, 1H), 1.46 (d, 7 = 6.3 Hz, 3H), 1.43 - 1.31 (m, 1H).

¹³ C NMR (101 MHz, CDCI3) δ 170.96, 170.26, 163.26, 160.20, 145.83, 143.88, 142.36, 139.58, 129.14, 128.50, 126.26,

109.66, 89.46, 76.26, 75.46, 74.38, 56.19, 53.89, 48.56, 38.42, 32.91, 20.88,

19.94.

*H NMR (400 MHz, CDCI3) δ 8.61 (d, 7 = 7.8 Hz, 1H), 8.29 (d, 7 = 5.4 Hz, 1H), 7.33 - 7.27 (m, 2H), 7.22 - 7.13 (m, 3H),

IR (thin

6.95 (d, 7 = 5.4 Hz, 1H), 5.78 - 5.70 (m, film)

2H), 5.09 (dq, 7 = 9.6, 6.5 Hz, 1H), 4.99 3379.55, HRMS-ESI (m/z)

(ddd, 7 = 7.8, 5.5, 4.2 Hz, 1H), 4.16 - 2938.34, ([M+HD calcd for

17 4.07 (m, 1H), 4.04 (dd, 7 = 11.5, 5.6 Hz, 1748.97, CietfeNiOs, 501.2231 ;

1H), 3.91 (s, 3H), 3.85 (dd, 7 = 11.5, 4.3 1675.29, found, 501.2233

Hz, 1H), 3.51 - 3.40 (m, 1H), 2.70 (ddd, 1503.70,

7 = 13.8, 10.3, 5.1 Hz, 1H), 2.55 (ddd, 7 1200.69

= 13.9, 10.3, 6.2 Hz, 1H), 2.07 (s, 3H), 1.86 - 1.65 (m, 4H), 1.62 - 1.51 (m, 1H), 1.34 (d, 7 = 6.3 Hz, 3H). ^* Cmpd. NMR

IR (cm ¹ ) MASS

No. (1H ¹³ C or ¹⁹ F)

*H NMR (400 MHz, CDCb) δ 8.53 (d,

IR (thin = 7.8 Hz, 1H), 8.26 (d, = 5.4 Hz, 1H), film) 7.36 - 7.27 (m, 4H), 7.21 - 7.12 (m, 1H), 3379.91, HRMS-ESI (m/z) 6.93 (d, = 5.4 Hz, 1H), 5.76 - 5.67 (m, 2962.74, ([M calcd for 2H), 4.93 - 4.83 (m, 2H), 3.96 (dd, =

18 +HD

1750.77, C28H37N2O8, 529.2544; 11.5, 5.4 Hz, 1H), 3.89 (s, 3H), 3.67 (dd, 1675.92, found, 529.2549 = 11.6, 4.9 Hz, 1H), 3.64 - 3.58 (m, 1501.71, 1H), 3.10 (ddd, = 12.5, 8.2, 2.0 Hz, 1200.41 1H), 2.05 (s, 3H), 1.61 - 1.44 (m, 5H),

1.35 (s, 6H), 1.16 (d, = 6.3 Hz, 3H).

IR (thin ^l H NMR (400 MHz, CDCb) δ 8.61 (d,

= 7.7 Hz, 1H), 8.29 (d, = 5.3 Hz, 1H), film)

6.95 (d, = 5.4 Hz, 1H), 5.78 - 5.69 (m, 3380.00,

HRMS-ESI (m/z) 2H), 5.10 - 4.93 (m, 2H), 4.11 - 3.99 (m, 2950.62,

([M+HD calcd for 2H), 3.91 (s, 3H), 3.84 (dd, = 11.5, 4.3

19 1747.22,

CisHssNiOs, 467.2388; Hz, 1H), 3.44 (ddd, / = 11.9, 8.4, 1.6 Hz, 1675.11,

found, 467.2388 1H), 2.07 (s, 3H), 1.71 - 1.57 (m, 2H), 1501.87,

1.57 - 1.43 (m, 2H), 1.42 - 1.28 (m, 1H), 1198.86,

1.35 (d, = 6.4 Hz, 3H), 1.25 - 1.11 (m, 964.68

3H), 0.92 - 0.81 (m, 6H).

MHz, CDCb) δ 8.61 (d,

IR (thin ^l H NMR (400

= 7.8 Hz, 1H), 8.29 (d, = 5.3 Hz, 1H), film)

6.95 (d, = 5.4 Hz, 1H), 5.78 - 5.68 (m, 3381.28,

HRMS-ESI (m/z) 2H), 5.03 - 4.91 (m, 2H), 4.10 - 4.01 (m, 2952.63,

([M calc 2H), 3.91 (s, 3H), 3.83 (dd, = 11.5, 4.4

20 1746.42, +HD d for

CnHssNiOs, 453.2231; Hz, 1H), 3.51 - 3.38 (m, 1H), 2.07 (s, 1675.30,

found, 453.2234 3H), 1.75 - 1.56 (m, 3H), 1.47 - 1.36 (m, 1502.16,

1H), 1.34 (d, = 6.3 Hz, 3H), 1.08 (dd, 1199.54,

= 7.6, 5.9 Hz, 2H), 0.91 (d, = 6.6 Hz, 965.70

3H), 0.87 (d, = 6.5 Hz, 3H).

*Cmpd. NMR

IR (cm ¹ ) MASS

No. (1H ¹³ C or ¹⁹ F)

*H NMR (400 MHz, CDCb) δ 8.77 (d,

IR (thin = 8.2 Hz, 1H), 8.34 (d, = 5.5 Hz, 1H), film) 7.00 (d, = 5.5 Hz, 1H), 5.03 (dq, = 3380.57, 9.7, 6.2 Hz, 1H), 4.96 (ddd, 7 = 8.1, 5.6, 2951.88, HRMS-ESI (m/z) 4.3 Hz, 1H), 4.09 - 4.03 (m, 1H), 4.01 1770.80, ([M calcd for (dd, = 11.5, 5.6 Hz, 1H), 3.90 (s, 3H),

21 +HD

1742.78, C22H33N2O7, 437.2282; 3.81 (dd, = 11.5, 4.4 Hz, 1H), 3.42 1676.22, found, 437.2288 (ddd, = 12.0, 8.4, 1.7 Hz, 1H), 2.39 (s, 1506.60, 3H), 1.71 - 1.56 (m, 2H), 1.56 - 1.42 (m, 1194.45, 2H), 1.41 - 1.28 (m, 1H), 1.34 (d, = 6.3 729.56 Hz, 3H), 1.23 - 1.09 (m, 3H), 0.88 (d,

= 5.2 Hz, 3H), 0.87 (d, = 5.1 Hz, 3H). lH NMR (400 MHz, CDCb) δ 8.77 (d,

IR (thin

= 8.1 Hz, 1H), 8.34 (d, = 5.4 Hz, 1H), film)

7.00 (d, = 5.5 Hz, 1H), 5.00 - 4.91 (m, 3380.48,

HRMS-ESI (m/z) 2H), 4.08 - 3.98 (m, 2H), 3.90 (s, 3H), 2953.74,

([M+HD calcd for 3.80 (dd, / = 11.5, 4.4 Hz, 1H), 3.44

22 1770.45,

C21H31N2O7, 423.2126; (ddd, = 12.0, 8.4, 1.6 Hz, 1H), 2.39 (s, 1741.89,

found, 423.2128 3H), 1.75 - 1.54 (m, 3H), 1.47 - 1.36 (m, 1506.35,

1H), 1.33 (d, = 6.3 Hz, 3H), 1.07 (dd, 1194.47,

= 7.6, 6.0 Hz, 2H), 0.91 (d, = 6.6 Hz, 729.42

3H), 0.87 (d, = 6.5 Hz, 3H). lH NMR (400 MHz, CDCb) δ 8.81 - 8.64 (m, 1H), 8.34 (d, = 5.4 Hz, 1H), 7.00 (d, = 5.4 Hz, 1H), 5.04 (dq, = 9.5, 6.3 Hz, 1H), 4.96 (ddd, 7 = 8.1, 5.6, 4.3 Hz, 1H), 4.07 (ddd, = 12.0, 6.6, 1.6 Hz, 1H), 4.01 (dd, J = 11.5, 5.6 Hz, 1H), 3.90 (s, 3H), 3.82 (dd, = 11.5, 4.3 Hz, 1H), 3.43 (ddd, = 12.0, 8.3, 1.8 Hz,

HRMS-FAB (m/z)

1H), 2.39 (s, 3H), 1.67 (ddt, = 15.6, ([M+HD calcd for

23 6.7, 1.6 Hz, 1H), 1.61 - 1.53 (m, 1H), 1.53 - 1.40 (m, 2H), 1.34 (d, = 6.3 Hz, found, 395.1816.

3H), 1.29 - 1.21 (m, 1H), 0.89 (t, = 7.4

Hz, 3H).

¹³ C NMR (101 MHz, CDCb) δ 170.97, 168.83, 162.71, 159.36, 146.77, 141.37,

137.45, 109.81, 76.32, 75.95, 74.53, 56.28, 53.62, 48.11, 33.74, 25.12, 20.73,

19.53, 10.40. *Cmpd. NMR

IR (cm ¹ ) MASS

No. (1H ¹³ C or ¹⁹ F)

*H NMR (400 MHz, CDCb) δ 8.61 (d, = 7.8 Hz, 1H), 8.29 (d, J = 5.3 Hz, 1H), 6.95 (d, J = 5.4 Hz, 1H), 5.74 (d, J = 1.6 Hz, 2H), 5.12 - 4.93 (m, 2H), 4.15 - 3.99 (m, 2H), 3.91 (s, 3H), 3.85 (dd, J = 11.5, 4.3 Hz, 1H), 3.44 (ddd, J = 12.1, 8.3, 1.8

HRMS-FAB im/z)

Hz, 1H), 2.07 (s, 3H), 1.73 - 1.38 (m, ([M+HD calcd for

24 4H), 1.35 (d, J = 6.3 Hz, 3H), 1.32 - 1.13

C20H29N2O8, 425.1924;

(m, 1H), 0.90 (t, J = 7.4 Hz, 3H). found, 425.1919.

¹³ C NMR (101 MHz, CDCb) δ 171.04, 170.22, 163.20, 160.16, 145.77, 143.86,

142.37, 109.57, 89.46, 76.29, 75.96, 74.50, 56.14, 53.83, 48.10, 33.71, 25.09,

20.84, 19.50, 10.36.

^X H NMR (400 MHz, CDCb) δ 7.38 - 7.09 (m, 10H), 5.76 (d, J = 7.7 Hz, 1H), 5.09 (s, 2H), 5.05 (ddd, J = 12.6, 7.8, 4.7 Hz, 1H), 4.63 (ddd, J = 7.7, 5.4, 3.9 Hz, 1H), 3.88 (dt, J = 12.4, 6.1 Hz, 2H), 3.74 (dd, J = 11.5, 4.0 Hz, 1H), 3.22 (ddd, J = 12.2, 8.2, 1.8 Hz, 1H), 2.81 (dd, J = 13.7,

ESIMS m/z 398

25 4.1 Hz, 1H), 2.23 (dd, J = 13.8, 10.4 Hz,

([Μ+ΗΓ)

1H), 2.00 - 1.87 (m, 1H), 1.63 (ddt, J =

16.4, 7.0, 2.1 Hz, 1H), 1.42 (d, J = 6.3 Hz, 3H), 1.39 - 1.27 (m, 1H). ¹³ C NMR

(101 MHz, CDCb) δ 171.04, 155.84, 139.57, 136.30, 129.16, 128.54, 128.16,

128.07, 126.32, 76.31, 75.56, 74.63, 66.98, 55.53, 48.65, 38.40, 32.79, 19.93.

^X H NMR (400 MHz, CDCb) δ 7.38 - 7.24 (m, 6H), 7.22 - 7.11 (m, 4H), 5.68

IR (thin

(d, J = 6.8 Hz, 1H), 5.10 (s, 2H), 5.04 film)

(dq, J = 9.3, 6.3 Hz, 1H), 4.61 (ddd, J = 3321.29, HRMS-ESI (m/z)

7.6, 5.5, 4.2 Hz, 1H), 4.10 - 4.04 (m, 2934.19, ([M+H] ⁺ ) calcd for

26 1H), 3.93 (dd, J = 11.5, 5.4 Hz, 1H), 3.77 1715.40, C24H30NO5, 412.2118;

(dd, J = 11.4, 4.0 Hz, 1H), 3.39 (ddd, J = 1497.01, found, 412.2121

12.2, 8.3, 1.9 Hz, 1H), 2.74 - 2.61 (m, 1200.34,

1H), 2.60 - 2.47 (m, 1H), 1.84 - 1.60 (m, 1047.60

3H), 1.58 - 1.46 (m, 2H), 1.32 (d, J = 6.3

Hz, 3H). *Cmpd. NMR

IR (cm ¹ ) MASS

No. (1H ¹³ C or ¹⁹ F)

IR (thin ^l H NMR (400 MHz, CDCI3) δ 7.40 - film) 7.27 (m, 9H), 7.21 - 7.12 (m, 1H), 5.56

HRMS-ESI (m/z)

3327.64, (d, J = 7.7 Hz, 1H), 5.08 (s, 2H), 4.84

[(M+Na) ⁺ ] calcd for

2960.83, (dq, J = 9.0, 6.1 Hz, 1H), 4.57 - 4.44 (m,

27 CietfeNNaOs,

1716.88, 1H), 3.99 - 3.76 (m, 2H), 3.64 - 3.53 (m,

462.2255; found,

1497.78, 1H), 3.17 - 2.91 (m, 1H), 1.59 - 1.41 (m,

462.2251

1198.57, 3H), 1.34 (s, 8H), 1.14 (d, J = 6.3 Hz, 1042.72 3H).

*H NMR (400 MHz, CDCI3) δ 7.42 - 7.29 (m, 5H), 5.63 (d, J = 7.8 Hz, 1H),

IR (thin 5.11 (s, 2H), 5.00 (dq, J = 9.7, 6.3 Hz, film) 1H), 4.67 - 4.56 (m, 1H), 4.03 (td, J =

HRMS-ESI (m/z)

3321.56, 13.3, 12.9, 6.5 Hz, 1H), 3.94 (dd, J =

([M+HD calcd for

28 2951.46, 11.5, 5.4 Hz, 1H), 3.76 (dd, J = 11.5, 4.2

C21H32NO5, 378.2275;

1716.07, Hz, 1H), 3.48 - 3.33 (m, 1H), 1.69 - 1.52 found, 378.228

1508.08, (m, 2H), 1.52 - 1.39 (m, 2H), 1.39 - 1.26 1039.89 (m, 1H), 1.33 (d, J = 6.3 Hz, 3H), 1.24 - 1.10 (m, 3H), 0.87 (d, J = 6.6 Hz, 3H), 0.86 (d, J = 6.5 Hz, 3H).

Cmpd. No. - Compound Number

lH NMR were run at 400 MHz unless noted otherwise.

¹³ C NMR were run at 101 MHz unless noted otherwise.

Table 3. Biological Testing Rating Scale

%DC - Percent Disease Control

Table 4. Biological Activity - PUCCRT and SEPTTR Disease Control at 100 ppm

Cmpd. No. - Compound Number

*PUCCRT - Wheat Brown Rust (Puccinia triticina)

*SEPTTR - Wheat Leaf Blotch {Zymoseptoria tritici)

*1DP - 1 Day Protectant

*3DC - 3 Day Curative

*ppm - Parts Per Million Table 5. Biological Activity - PUCCRT and SEPTTR Disease Control at 121.5 g/H

Cmpd. No. - Compound Number

*PUCCRT - Wheat Brown Rust {Puccinia triticina)

*SEPTTR - Wheat Leaf Blotch {Zymoseptoria tritici)

*1DP - 1 Day Protectant

*3DC - 3 Day Curative

*g/H - Grams Per Hectare

Table 6. Biological Activity - PHAKPA Disease Control at 25 ppm

Cmpd. No. - Compound Number

^* PHAKPA - Asian Soybean Rust {Phakopsora pachyrhizi) *1DP - 1 Day Protectant

*3DC - 3 Day Curative