| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | October 26, 1999 |
| PATENT TITLE |
4-cyano-4-deformylsordarin derivatives |
| PATENT ABSTRACT | 4-Cyano-4-deformylsordarin derivatives are antifungal agents useful in the treatment and/or prevention of human and animal fungal infections, as well as in the control of phytopathogenic fungi in crops |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | July 28, 1998 |
| PATENT REFERENCES CITED |
von D. Hauser, et al., Helvetica Chimica Acta--vol. 54, Fasc. 4, pp. 1178-1190, 1971. Stephen Coval, et al., J. Antibiotics, vol. 48, pp. 1171-1172, 1995. Lewis Mander, et al., J. Org. Chem. vol. 56, pp. 3595-3601, 1991. Nobuo Kato, et al., J. Chem. Soc., Chem. Commun., pp. 1002-1004, 1993. |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
What is claimed is: 1. A compound having the formula I: ##STR48## and wherein Z is a tetrahydropyrano group selected from ##STR49## and salts and solvates (e.g. hydrates) or metabolically labile derivatives thereof, wherein R.sup.a is C(O)CH.sub.3 or CH.sub.3 ; R.sup.1 is hydrogen, halogen, hydroxyl, C.sub.1-4 alkoxy or acyloxy; R.sup.2 and R.sup.3 are each independently hydrogen, C.sub.1-6 alkyl or C.sub.1-4 alkoxy C.sub.1-4 alkyl, or R.sup.2 and R.sup.3 together with the carbon atom to which they are attached represent C.dbd.O, C.dbd.S or C.sub.3-8 cycloalkyl; R.sup.4 is hydrogen or CH.sub.2 R.sup.7 (where R.sup.7 is hydrogen, hydroxyl, C.sub.1-4 alkoxy or a group OCOR.sup.8 in which R.sup.8 is C.sub.1-4 alkyl or aryl); R.sup.5 and R.sup.6 are each independently hydrogen, C.sub.1-6 alkyl or C.sub.1-4 alkoxy C.sub.1-4 alkyl, or R.sup.5 and R.sup.6 together with the carbon atom to which they are attached represent C.dbd.O, C.dbd.S or C.sub.3-8 cycloalkyl; n is zero or 1; X and Y are each independently oxygen, sulfur or CR.sup.9 R.sup.10 (where R.sup.9 and R.sup.10 are each independently hydrogen, C.sub.1-6 alkyl, C.sub.1-4 alkoxy or C.sub.1-4 alkoxyC.sub.1-14 alkyl; or R.sup.9 and R.sup.10 together with the carbon atom to which they are attached represent C.dbd.O, C.dbd.S, C.sub.3-8 cycloalkyl or C.dbd.CHR.sup.11 where R.sup.1 represents hydrogen or C.sub.1-4 alkyl); or when X or Y is oxygen and n is zero then --Y--CR.sup.2 R.sup.3 or --X--CR.sup.2 R.sup.3 -- respectively may also represent --N.dbd.CR.sup.3 -- or --NR.sup.12 --CR.sup.2 R.sup.3 -- (where CR.sup.2 and R.sup.3 are C.dbd.O and R.sup.12 is C.sub.1-4 alkyl an acyl group COR.sup.13 where R.sup.13 is C.sub.1-6 alkyl) or when Y is oxygen and n is zero X may be represent the group CR.sup.11 (wherein R.sup.11 has the meanings defined above) which is attached to the pyran ring by a double bond; R.sup.15 is hydrogen, halogen, azido, C.sub.1-6 alkyl, hydroxy, C.sub.1-6 alkoxy (optionally substituted by 1 or 2 hydroxy or a ketal thereof or 1 or 2 C.sub.1-3 alkoxy groups), arylC.sub.1-4 alkoxy, C.sub.3-6 alkenyloxy, a group OCOR.sup.18 (where R.sup.18 is arylC.sub.1-4 alkoxy or a C.sub.1-10 alkyl group optionally containing one or two double bonds) or C.sub.1-6 alkoxycarbonyl C.sub.1-4 alkoxy, and R.sup.16 represents hydrogen or R.sup.15 and R.sup.16 may together with the carbon atom to which they are attached represent C.dbd.O or C.dbd.CH.sub.2 ; R.sup.17 is CH.sub.2 R.sup.19 where R.sup.19 is hydrogen, hydroxyl, C.sub.1-14 alkoxy or a group OCOR.sup.20 in which R.sup.20 is C.sub.1-4 alkyl); and W is oxygen, sulfur, or CH.sub.2 ; and the dotted line in group (a) indicates the optional presence of an additional bond; R.sup.1a is hydrogen, halogen, hydroxyl or C.sub.1-4 alkoxy; R.sup.2a is hydrogen, halogen, hydroxyl, C.sub.1-10 alkoxy, C.sub.1-10 alkylthio, C.sub.1-6 alkoxyC.sub.1-4 alkoxy, arylC.sub.1-6 alkyloxy, arylC.sub.3-6 alkenyloxy, azido, NR.sup.5a COR.sup.5a (where each R.sup.5a is independently hydrogen or C.sub.1-6 alkyl), OR.sup.6a (where R.sup.6a is a cyclic ether containing 4 to 8 atoms linked to the oxygen atom via a ring carbon atom adjacent to the ring oxygen atom) or a group Y.sup.a C(.dbd.O)--X.sup.a --R.sup.7a where Y.sup.a is oxygen, sulfur or NH, X.sup.a is either a bond, an oxygen atom or a moiety NR.sup.8a in which R.sup.8a is hydrogen or C.sub.1-6 alkyl, and R.sup.7a is C.sub.1-10 alkyl optionally containing one or two double bonds, aryl, arylC.sub.1-4 alkyl, arylC.sub.2-4 alkenyl, haloC.sub.1-6 alkyl, or C.sub.1-6 alkoxyC.sub.1-4 alkyl), and R.sup.3a represents hydrogen, or R.sup.2a and R.sup.3a together with the carbon atom to which they are attached represent C.dbd.O or C.dbd.NOR.sup.9a (where R.sup.9a is C.sub.1-6 alkyl); and R.sup.4 a is hydroxyl, C.sub.1-6 alkoxy or OC(.dbd.O)R.sup.7a (where R.sup.7a is as defined above). 2. A compound of claim 1 with the following structural formula: ##STR50## 3. A compound of claim with the following structural formula: 4. A compound of claim 1 with the following structural formula: 5. A compound of claim 1 with the following structural formula: 6. A compound of claim 1 with the following structural formula: 7. A compound of claim 1 with the following structural formula: 8. A compound of claim 1 with the following structural formula: 9. A pharmaceutical composition which comprises a compound of claim 1 and a pharmaceutically acceptable carrier. 10. An agrochemical composition which comprises a compound of claim 1 and a agriculturally acceptable carrier. 11. A method for the treatment or prevention of fungal infection in an animal which comprises adminstering to said animal an antifungal effective amount of a compound of claim 1. 12. A method for controlling phytopathogenic fungi which comprises administering to a plant in need of such control an antifungal effective amount of a compound of claim 1. 13. A method for the preparation of 4-cyano-4-deformyl-4'-demethyl sordarin which comprises: contacting 4-cyano-4-deformylsordarin with a culture of a strain of Streptomyces avermitilis in a fermentation medium containing assimilable sources of carbon and nitrogen; and isolating 4-cyano-4-deformyl-4'-demethyl sordarin from said fermentation medium. -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
SUMMARY OF THE INVENTION The present invention relates to 4-cyano-4-deformylsordarin derivatives which are potent antifungal agents with a broad spectrum of activity and increased stability, to processes for their preparation, to pharmaceutical and agricultural compositions containing the compounds, and to methods of controlling fungal infections in human, animals and plant materials using such compounds. BACKGROUND OF THE INVENTION Sordarin is an antifungal antibiotic isolated from the mould Sordaria araneosa (see GB 1,162,027 and Helvetica Chimica Acta, 1971, 51:119-20). Other compounds having the sordarin skeleton have also been reported as antifungal agents. Japanese Kokai J62040292 discloses the compound zofimarin isolated from Zofiela marina sp.; Japanese Kokai J06157582 discloses the compound BE-31405 isolated from Penicillium sp.; and SCH57404 is reported in J. Antibiotics, 1995, 48:1171-1172. Semi-synthetic sordarin derivatives are reported in PCT Applications WO96/14326 and WO96/14327. DETAILED DESCRIPTION OF THE INVENTION The present invention provides compounds having the formula (I): ##STR1## and wherein Z is a tetrahydropyrano group selected from ##STR2## and salts and solvates (e.g. hydrates) or metabolically labile derivatives thereof, wherein R.sup.a is C(O)CH.sub.3 or CH.sub.3 ; R.sup.1 is hydrogen, halogen, hydroxyl, C.sub.1-4 alkoxy or acyloxy; R.sup.2 and R.sup.3 are each independently hydrogen, C.sub.1-6 alkyl or C.sub.1-4 alkoxy C.sub.1-4 alkyl, or R.sup.2 and R.sup.3 together with the carbon atom to which they are attached represent C.dbd.O, C.dbd.S or C.sub.3-8 cycloalkyl; R.sup.4 is hydrogen or CH.sub.2 R.sup.7 (where R.sup.7 is hydrogen, hydroxyl, C.sub.1-4 alkoxy or a group OCOR.sup.8 in which R.sup.8 is C.sub.1-4 alkyl or aryl); R.sup.5 and R.sup.6 are each independently hydrogen, C.sub.1-6 alkyl or C.sub.1-4 alkoxy C.sub.1-4 alkyl, or R.sup.5 and R.sup.6 together with the carbon atom to which they are attached represent C.dbd.O, C.dbd.S or C.sub.3-8 cycloalkyl; n is zero or 1; X and Y are each independently oxygen, sulfur or CR.sup.9 R.sup.10 (where R.sup.9 and R.sup.10 are each independently hydrogen, C.sub.1-6 alkyl, C.sub.1-4 alkoxy or C.sub.1-4 alkoxyC.sub.1-4 alkyl; or R.sup.9 and R.sup.10 together with the carbon atom to which they are attached represent C.dbd.O, C.dbd.S, C.sub.3-8 cycloalkyl or C.dbd.CHR.sup.11 where R.sup.11 represents hydrogen or C.sub.1-4 alkyl); or when X or Y is oxygen and n is zero then --Y--CR.sup.2 R.sup.3 or --X--CR.sup.2 R.sup.3 -- respectively may also represent --N.dbd.CR.sup.3 -- or --NR.sup.12 --CR.sup.2 R.sup.3 -- (where CR.sup.2 and R.sup.3 are C.dbd.O and R.sup.12 is C.sub.1-4 alkyl an acyl group COR.sup.13 where R.sup.13 is C.sub.1-6 alkyl) or when Y is oxygen and n is zero X may be represent the group CR.sup.11 (wherein R.sup.11 has the meanings defined above) which is attached to the pyran ring by a double bond; R.sup.15 is hydrogen, halogen, azido, C.sub.1-6 alkyl, hydroxy, C.sub.1-6 alkoxy (optionally substituted by 1 or 2 hydroxy or a ketal thereof or 1 or 2 C.sub.1-3 alkoxy groups), arylC.sub.1-4 alkoxy, C.sub.3-6 alkenyloxy, a group OCOR.sup.18 (where R.sup.18 is arylC.sub.1-4 alkoxy or a C.sub.1-10 alkyl group optionally containing one or two double bonds) or C.sub.1-6 alkoxycarbonyl C.sub.1-4 alkoxy, and R.sup.16 represents hydrogen or R.sup.15 and R.sup.16 may together with the carbon atom to which they are attached represent C.dbd.O or C.dbd.CH.sub.2 ; R.sup.17 is CH.sub.2 R.sup.19 where R.sup.19 is hydrogen, hydroxyl, C.sub.1-14 alkoxy or a group OCOR.sup.20 in which R.sup.20 is C.sub.1-4 alkyl); and W is oxygen, sulfur, or CH.sub.2 ; and the dotted line in group (a) indicates the optional presence of an additional bond; R.sup.1a is hydrogen, halogen, hydroxyl or C.sub.1-4 alkoxy; R.sup.2a is hydrogen, halogen, hydroxyl, C.sub.1-10 alkoxy, C.sub.1-10 alkylthio, C.sub.1-6 alkoxyC.sub.1-4 alkoxy, arylC.sub.1-6 alkyloxy, arylC.sub.3-6 alkenyloxy, azido, NR.sup.5a COR.sup.5a (where each R.sup.5a is independently hydrogen or C.sub.1-6 alkyl), OR.sup.6a (where R.sup.6a is a cyclic ether containing 4 to 8 atoms linked to the oxygen atom via a ring carbon atom adjacent to the ring oxygen atom) or a group Y.sup.a C(.dbd.O)--X.sup.a --R.sup.7a where Y.sup.a is oxygen, sulfur or NH, X.sup.a is either a bond, an oxygen atom or a moiety NR.sup.8a in which R.sup.8a is hydrogen or C.sub.1-6 alkyl, and R.sup.7a is C.sub.1-10 alkyl optionally containing one or two double bonds, aryl, arylC.sub.1-4 alkyl, arylC.sub.2-4 alkenyl, haloC.sub.1-6 alkyl, or C.sub.1-6 alkoxyC.sub.1-4 alkyl), and R.sup.3 a represents hydrogen, or R.sup.2a and R.sup.3a together with the carbon atom to which they are attached represent C.dbd.O or C.dbd.NOR.sup.9a (where R.sup.9a is C.sub.1-6 alkyl); and R.sup.4 a is hydroxyl, C.sub.1-6 alkoxy or OC(.dbd.O)R.sup.7a (where R.sup.7a is as deemed above). One embodiment of the present invention provides compounds of formula I wherein ##STR3## In another aspect of the present invention, there is provided a pharmaceutical composition which comprises an antifungal effective amount of a compound of formula I, and a pharmaceutically acceptable carrier. Also provided is a pharmaceutical composition which is made by combining a compound of formula I and a pharmaceutically acceptable carrier. Another aspect of the present invention provides an agricultural composition which comprises an antifungal effective amount of a compound of formula I, and an agriculturally acceptable carrier thereof. Also provided is an agricultural composition which is made by combining a compound of formula I and an agriculturally acceptable carrier. Yet another aspect of the present invention provides a method for treating fungal infection in an animal (including humans) which comprises administering to an animal in need of such treatment an antifungal effective amount of a compound of formula I. A further aspect of the present invention provides a method for controlling phytopathogenic fungi in plants which comprises applying to said plant an antifungal effective amount of a compound of formula I. In the application, unless otherwise specified, the following definitions apply: The term "control" or "controlling" includes prophylactic use (i.e. to protect against infection) and curative use (i.e. to eradicate infection). The term "plants" include whole live plants or parts thereof, foliage, flowers, seeds, fruits, and other materials derived from plants. The term also includes roots of the plant via application of the active ingredient to the soil. The term "composition", as in agricultural or agrochemical composition, is intended to encompass a product comprising the active ingredient(s), and the inert ingredient(s) that make up the carrier, as well as any product which results, directly or indirectly, from combination, complexation or aggregation of any two or more of the ingredients, or from dissociation of one or more of the ingredients, or from other types of reactions or interactions of one or more of the ingredients. Accordingly, the compositions of the present invention encompass any composition made by admixing a compound of the present invention and an agriculturally acceptable carrier. "Alkyl" as a group or part of a group means a straight or branched chain alkyl moiety such as methyl, ethyl, n-propyl, n-butyl, isopropyl, s-butyl, t-butyl, n-hexyl and n-octyl. "Aryl" as a group or part of a group means phenyl or heteroaryl each optionally substituted by one to three groups independently selected from halogen, hydroxyl, C.sub.1-6 alkyl, C.sub.1-6 alkoxy or C.sub.1-4 alkoxycarbonyl. The heteroaryl group may be a 5- or 6-membered heteroaromatic ring containing one or more heteroatoms selected from nitrogen, oxygen and sulfur. Suitable examples of heteroaryl groups include pyridyl, furyl, thienyl and pyrrolyl. "Halogen" or "halo" means fluorine, chlorine, bromine or iodine. When R.sup.1 is an acyloxy group it may represent, for example a group OCOR.sup.13 where R.sup.13 is as defined above. Suitable salts of a compound of formula I include inorganic base salts such as alkali metal salt (e.g. sodium and potassium salts), ammonium salts, and organic base salts. Suitable organic base salts include amine salts such as trialkylamine (e.g. triethylamine), dialkylamine salts (e.g. dicyclohexylamine), optionally substituted benzylamine (e.g. phenylbenzylamine or p-bromobenzylamine), ethanolamine, diethanolamine, N-methylglucosamine, N-methylpiperidine, pyridine and substituted pyridine (e.g. collidine, lutidine, 4-dimethylaminopyridine), and tri(hydroxymethyl)methylamine salts, and amino acid salts (e.g. lysine or arginine salts). Metabolically labile derivatives of compounds of formula I are compounds which are converted in the subject being treated (be it an animal, a plant (including foliage, flower, fruit, seed, or other parts or product of the plant), or soil) into compounds of formula I. Examples of such derivatives include conventional metabolically labile esters formed from the carboxylic acid in the molecule. Preparation of Compounds. Compounds of formula I may be prepared from sordarin and derivatives thereof, sordaricin, and other sordarin type compounds, which all have been described in the literature. Sordarin is [1R-(1.alpha.,3a.beta.,4.beta.,4a.beta.,7.beta.,7a.alpha.,8a.beta.)] 8a-[(6-deoxy-4-O-methyl-.beta.-D-altropyranosyloxy)methyl] -4-formyl-4,4a,5,6,7,7a,8,8a-octahydro-7-methyl-3-(1-methylethyl)-1,4-meth ano-s-indacene-3a(1H)-carboxylic acid having the formula II: ##STR4## Sordarin can be obtained by the cultivation of Sodaria araneosa NRRL 3196 (also deposited with the ATCC as ATCC 36386) according to the procedure described in GB1,162,027 or in WO96/14326. Sordarin can also be isolated from the fermentation of Rosellinia subiculata and an unidentified fungus ATCC 74387 as described hereinbelow. Zofimarin may be obtained from the fermentation broth of Zofiela marina SANK 21274 (ATCC 34456) as described in Japanese Kokai 62040292. BE31405 (I, wherein A is (f) and R.sup.a is acetyl) is produced by Penicillum sp. F31405 as described in Japanese Kokai 06157582. SCH.sub.57404 (I, wherein A is (f) and R.sup.a is methyl) is produced by a fungus identified as Schering culture number SCF1082A as reported in J. Antibiotics, 1995, 48(10):1171-1172. Starting materials for sordarin derivatives (I, wherein Z is (a) or (b)), are described in PCT Application WO96/14326; and starting materials for sordarin derivatives (I, wherein Z is (c)) are described in PCT Application WO96/14327. Sordaricin (VI) is [1R-(1.alpha.,3a.beta.,4.beta.,4a.beta.,7.beta.,7a.alpha.,8a.beta.)] 4-formyl-8a-(hydroxymethyl)-4,4a,5,6,7,7a,8,8a-octahydro-7-methyl-3-(1-met hylethyl)-1,4-methano-s-indacene-3a(1H)-carboxylic acid having the formula VI: ##STR5## Sordaricin can be prepared from sordarin by treatment with concentrated hydrochloric acid. As disclosed in WO96/14326 sordaricin is also obtained from fermentation of a mutant derived from Sordaria araneosa NRRL 3196, and by biotransformation of sordarin using a Coryneform species. As mentioned above, two other organisms have been found to produce sordarin. One of the fungal strains used to produce sordarin is an unidentified sterile fungus GB3109 that was isolated from the internal tissues of roots of a mangrove shrub, Conocarpus erectus (Combretaceae), collected in the Manglar de Reo Rincon, Peninsula de Osa, Provincia de Puntarenas, Costa Rica, and identified as MF6232 in the culture collection of Merck & Co., Inc., Rahway, N.J. This culture was deposited on Aug. 27, 1996 in the permanent collection at the American Type Culture Collection, 12301 Parklawn Drive, Rockville, Md. 20852, USA under the terms of The Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure, and assigned the accession number ATCC 74387. The fungus was grown on a variety of mycological media, under different light regimes, and on sterilized leaves and filter paper but in all cases, it has failed to produce reproductive structures and thus cannot be identified. In agar culture, colonies of the fungus exhibit the following morphology: Colonies on oatmeal agar (Difco) at 23.degree. C., 12 hr photoperiod, growing moderately fast, attaining 85-90 mm in 14 days, with advancing zone appressed, even, obscurely zonate, strongly radially striate, with moist appressed mycelium at the center, becoming silky with radiating prostrate hyphal bundles or strands, translucent to pale pink, near Pale Ochraceous Salmon (capitalized color names from Ridgway, R. 1912. Color Standards and Nomenclature, Washington, D.C.), Light Ochraceous Salmon, pinkish gray Avellaneous, Cinnamon-Drab, or white in uppermost aerial mycelium, reverse pale pinkish gray, exudates absent, odor faintly fragrant. No growth at 37 C on oatmeal agar. Colonies on V8 juice agar (Stevens, R. B. 1981. Mycology Guidebook. University of Washington Press, Seattle, pg. 665) at 23.degree. C., 12 hr photoperiod, growing slowly attaining 37-42 mm in 14 days, submerged to at the margin, mostly with appressed most mycelium, with some scant floccose aerial mycelium towards outer third, zonate, translucent to pale grayish pink, similar to color on oatmeal agar, reverse translucent to pale reddish brown, near Wood Brown, Fawn Color. Colonies on cornmeal agar (Difco) at 25.degree. C., 12 hr photoperiod, growing slowly, attaining 33-34 mm in 14 days, with margin submerged, lacking aerial hyphae, zonate, translucent. The mycelium is composed of highly branched, simple septate, hyaline hyphae. The second fungal strain (GB3719) used to produce sordarin is a strain of Rosellina subiculata (Ascomycotina, Xylariaceae), designated as MF6239 in the culture collection of Merck & Co., Inc., Rahway, N.J. This culture was deposited on Aug. 27, 1996 in the permanent collection at the American Type Culture Collection, 12301 Parklawn Drive, Rockville, Md. 20852, USA under the terms of The Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure, and assigned the accession number ATCC 74386. Ascomata of Rosellinia subiculata (GB3719) were found on a decorticated hardwood limb on the shore of the Navesink River, Monmouth Co., N.J. In the laboratory, the apices of several ascomata were removed with a sterilized microtome blade and asci, paraphyses and ascospores from the centrum were removed with an insect pin and streaked onto malt-yeast extract agar. Ascospores were incubated overnight until they germinated and were transferred to tubes of malt-yeast extract agar to initiate pure colonies. The morphology of Rosellinia subiculata (GB3719) generally conformed to descriptions in the literature (J. B. Ellis & B. M. Everhart. 1892. The North American Pyrenomycetes. Published by the authors, Newfield, N.J. pg. 165-166; L. E. Petrini. 1993. Rosellinia species of the temperate zones. Sydowia 44:169-281). The key features that lead to identification of the fungus as Rosellinia subiculata were: stromatic ascomata occurring singly but aggregated or fused in small clusters on a mycelial subiculum on decorticated wood; stromata were hemispherical, papillate, smooth, shiny, black, subiculum a thin mycelial mat, pale buff, or sometimes appearing only as a lightly colored discoloration of the wood adjacent to the stromata; asci were cylindrical with an amyloid apical plug; ascospores were brownish gray, broadly elliptical to slightly reniform, smooth, without appendages or sheaths, with a straight, ventral germ slit, 10-12.times.5-6 .mu.m. In agar culture, colonies of the fungus exhibit the following morphology: Colonies on oatmeal agar at 23.degree. C., 12 hr photoperiod, growing moderately fast, attaining 73-75 mm in 14 days, with advancing zone appressed, even, obscurely zonate, with white velvety to floccose mycelium over inner third, with moist appressed mycelium over outer two-thirds, translucent to white or pale pink, pale vinaceous pink, Light Vinaceous Cinnamon in reverse, exudates absent, slightly fragrant odor. No growth at 37 C on oatmeal agar. Colonies on V8 juice agar at 23.degree. C., 12 hr photoperiod, growing slowly attaining 25-35 mm in 14 days, submerged at the margin, mostly with appressed most mycelium, with some floccose aerial mycelium towards inner third, zonate, translucent to pale grayish pink, Vinaceous Cinnamon, reverse translucent to cinnamon, Orange-Cinnamon, Cinnamon, or pale reddish brown, Russet, Fawn Color, odor fragrant. Colonies on cornmeal agar at 25.degree. C., 12 hr photoperiod, growing slowly, attaining 29-34 mm in 14 days, with margin submerged, lacking aerial hyphae, azonate, translucent, or with scant white mycelium at inoculation point, colorless in reverse. When first grown in culture in August of 1993, the strain produced scant conidiophores and conidia of a Geniculosporium anamorph similar to that described by Petrini 1993. However, sporulation is no longer apparent, most likely due to prolonged storage and repeated transfers. At least in one case, a few mature perithecia with asci and ascospores identical to those observed in nature were formed after 5 weeks growth on oatmeal agar. Ascospores germinated overnight when incubated on malt-yeast extract agar at rom temperature. The mycelium is composed of highly branched, simple septate, hyaline hyphae. Sordarin is produced by cultivating a strain of Rosellina subiculata or the unidentified fungus MF6232 (ATCC.sub.74387) capable of producing said compound on a conventional solid medium or in a conventional aqueous medium. The organism is grown in a nutrient medium containing known nutritional sources for similar fungi, i.e. assimilable sources of carbon and nitrogen plus optional inorganic salts and other known growth factors. The general procedures used for the cultivation of other similar fungi are applicable to the present invention. The nutrient medium should contain an appropriate assimilable carbon source such as ribose, glucose, sucrose, cellobiose or fructose. As nitrogen source, ammonium chloride, ammonium-sulfate, urea, ammonium nitrate, sodium nitrate, etc. may be used either alone or in combination with organic nitrogen sources such as peptone, fish meal extract, yeast extract, corn steep liquor, soybean powder, cotton seed flour, etc. There may also be added, if necessary, nutrient inorganic salts to provide sources of sodium, potassium, calcium, anammonium, phosphate, sulfate, chloride, bromide, carbonate, zinc, magnesium, manganese, cobalt, iron, and the like. Production of sordarin may be effected at any temperature conducive to satisfactory growth of the producing organism, e.g. 20.degree.30.degree. C. Ordinarily, optimum production of the desired compound is obtained in shake flasks after incubation periods of 7-21 days. Aeration in shake flasks is achieved by agitation, e.g. shaking on a rotary shaker. If fermentation is to be carried out in tank fermentors, it is desirable to produce a vegetative inoculum in a nutrient broth by inoculating the broth culture from slant culture, lyophilized culture or frozen culture of the organism. After obtaining an active inoculum in this manner, it is aseptically transferred to the fermentation tank medium. Production of the desired compound in tank fermentors usually reaches the optimum after 7 to 21 days of incubation. Agitation in the tank fermentor is provided by stirring and aeration may be achieved by injection of air or oxygen into the agitated mixture. Compound production may be monitored using chromatographic or spectroscopic techniques, or by a conventional biological assay. Sordarin is readily recovered from fermentation broth by extracting the whole broth with an organic solvent such as methyl ethyl ketone. The compounds may be purified using standard methods well known in the art such as gel filtration chromatography, thin layer chromatography, high performance liquid chromatography, concentration, precipitation and/or crystallization, or combinations thereof. Alternatively, the whole broth or an organic extract thereof may be spray-dried or freeze-dried, followed by purification as above mentioned. The compounds of the present invention (formula I) may be prepared by the processes described below. The conditions are representative and are not intended to be limiting. As illustrated in Scheme 1, compounds of Formula I where Z is (a) or (b) may be prepared from starting materials described in PCT Application WO96/14326 or from starting materials described in PCT Application WO96/14327 for compounds of Formula I where Z is (c). The carboxylic acid of the starting material is derivatized with a suitable protecting group (i.e. benzyl or p-methoxybenzyl) and an aldoxime is formed by treatment with hydroxylamine hydrochloride in an alcoholic solvent containing pyridine. The aldoxime is transformed into a nitrile group with a suitable dehydrating agent (i.e. (methoxycarbonylsulfamoyl)-triethylammonium hydroxide inner salt or cyanuric chloride) and the protecting group is removed to yield a compound of formula (I). ##STR6## A compound of formula I(d) may be prepared as illustrated in Scheme 2. Sordarin is suitably protected and the aldehyde is reacted with hydroxylamine hydrochloride in an alcoholic solvent in the presence of pyridine. The resultant aldoxime is dehydrated with a reagent such as (methoxycarbonylsulfamoyl)-triethylammonium hydroxide inner salt or cyanuric chloride to give the nitrile compound (IV). Removal of the protecting groups (PG) gives the compound of formula I(d). ##STR7## Scheme 3 shows the microbial demethylation of the 4'-methoxy group of compound I(d) to provide Compound (V). The demethylation is accomplished by contacting a compound of formula I(d) with a culture of a strain of Streptomyces avermitilis in a fermentation medium containing assimilable sources of carbon and nitrogen; and isolating compound (V) from the fermentation medium. Suitable strains of Streptomyces avermitilis includes strain MA4848 deposited at American Type Culture Collection, Rockville, Md. as ATCC 31272. Compound (V) may be employed in the synthesis of compounds of formula (I). ##STR8## Alternatively, as shown in Scheme 4, sordaricin (VI) may be employed as a starting material for the synthesis of compounds of formula (I). Derivatization of the carboxylic acid with a suitable protecting group followed by protection of the primary hydroxyl group allows the synthesis of the nitrile-aglycone compound (VII) by reaction with hydroxylamine hydrochloride followed by dehydration and removal of the hydroxy protecting group. Attachment of a suitable sugar or modified sugar substrate by methods known to those skilled in the art, provide compounds of formula (I). ##STR9## Utility. Compounds of formula I are antifungal agents useful as human and animal medicaments, as well as crop protectants. The compounds of formula I are very active fungicides useful in combating fungal infections in animals, including humans. For example, they may be used in the treatment of fungal infections caused by organisms such as species of Candida (e.g. Candida albicans, Candida glabrata, (Torulopsis glabrata), Candida tropicalis, and Candida pseudotropicalis), Cryptococcus neoformans, Pneumocystis carinii, Aspergillus Sp (e.g. Aspergillus flavus and Aspergillus fumigatus), Coccidioides (e.g. Coccidioides immitis), Paracoccidioides (e.g. Paracoccidioides brasiliensis), Histoplasma (e.g. Histoplasma capsulatum) or Blastomyces (e.g. Blastomyces dermatitidis). They may also be used to treat other fungal infections caused by species of Trichophyton, Microsporum or Epidermophvton (e.g. Trichophyton mentographytes, Trichophyton rubrum, Microsporum canis or Epidermophyton floccosum), or in mucosal infections caused by Candida albicans. Compounds of formula I may also be used to treat other infections caused by species of filamentous fungi such as Geotrichum (e.g. Geotrichum clavatum), Trichosporon (e.g. Trichosporon beiglii), Blastoschizomyces (e.g. Blastoschizomyces capitatus), Sporothrix (e.g. Sporothrix schenckii), Scedosporium (e.g. Scedosporium apiosperum), Cladosporium (e.g. Cladosporium carrionii) and Pityrosporum ovale. The compounds of formula I may also be used to treat infections caused by protozoa such as Toxoplasma, Cryptosporidium, Leishmania, Tripanosoma, Giardia and Trichomonas. The in vitro evaluation of the anti-fungal activity of compounds of the invention was performed on liquid or solid medium by the anti-fungal two-fold serial dilution technique of determining the minimum inhibitory concentration (MIC) of anti-fungal agent that inhibited development of growth after 24 to 48 hours of incubation at 35.degree. C. In practice, a series of agar plates or broth microdilution panels containing two-fold dilutions of anti-fungal agent tested were inoculated with a standard culture of a clinically relevant pathogen, for example, Candida albicans. The agar plates or broth microdilution panels were then examined for the presence or absence of growth of the fungus and the appropriate MIC values were noted. Visualization of endpoints was assisted by employment of the vital stain Alamar Blue. The in vivo evaluation of compounds of formula I can be carried out at a series of dose levels by administration (e.g. subcutaneously, orally, intraperitoneally or intravenously) to mice inoculated intravenously with a strain of Candida spp. The kidneys of the test animals may be removed and quantitated for viable Candida spp. and the reduction in infection may be determined relative to untreated control animals. In view of their antifungal activity, compounds of formula I are useful for the treatment and/or prevention of a variety of fungal infections in human beings and animals. Such infections include superficial, cutaneous, subcutaneous and systemic mycotic infections such as respiratory tract infections, gastrointestinal tract infections, cardiovascular infections, urinary tract infections, CNS infections, candidiasis and chronic mucocandidiasis (e.g. thrush and vaginal candidiasis) and skin infections caused by fungi, cutaneous and mucocutaneous candidiasis, dermatophytoses including ringworm and tinea infections, athletes foot, paronychia, pityriasis versicolor, erythrasma, intertrigo, fungal diaper rash, candida vulvitis, candida balanitis and otitis externa. They may also be used as prophylactic agents to prevent systemic and topical fungal infections. Use as prophylactic agents may, for example, be appropriate as part of a selective gut decontamination regimen in the prevention of infection in immunocompromised patients (e.g. AIDS patients, patients receiving cancer therapy or transplant patients). Prevention of fungal overgrowth during antibiotic treatment may also be desirable in some disease syndromes or iatrogenic states. Compounds of formula I also have use as broad spectrum crop antifungal agents and are effective on a broad spectrum of phytopathogenic fungi, in particular those from the class consisting of: Deuteromycetes (e.g. Botrytis spp., Septoria spp., Pyricularia spp., Stagnospora spp., Helminthosporium spp., Fusarium spp., Cercospora spp., Rhynchosporium, spp. Pseudocercosporella, spp. and Alternaria spp.); Basidiomycetes (e.g. Puccinia spp., Rhizoctonia spp., and Hemileia); Ascomycetes (e.g. Venturia spp., Podospharera spp., Erysiphe spp., Monilinia spp. and Uncinula spp.); and Oomycetes (e.g. Phytophthora spp., Pemospora spp., Bremia spp., Pythium spp., and Plasmopara spp.). The foregoing list exemplifies the phytopathogenic fungi against which the named compounds demonstrate activity, and is not limiting in any manner. These compounds have very advantageous curative and preventive fungicidal properties for protecting plants, and can be used to inhibit or to destroy the microorganisms occurring on plants or on parts of plants (the fruit, blossom, leaves, stalks, tubers or roots) of different crops of useful plants, while at the same time parts of plants that grow later are also protected against such microorganisms. They can also be used as dressings in the treatment of plant propagation material, especially seed (fruit, tubers, grain) and plant cuttings (for example rice), to provide protection against fungal infections and against phytopathogenic fungi occurring in the soil. Compounds of formula I of the invention are distinguished by the fact that they are especially well tolerated by plants and are environmentally friendly. Agricultural evaluation of compounds of formula I can be carried out using the following tests. 1. Action against Erysiphe graminis on wheat. a) After 1 week cultivation, wheat plants are sprayed to run off with a spray mixture (200 ppm active ingredient/20% acetone/0.25% Triton X155). After 2 hours, the treated plants are infected with ascospores shaken from inoculum plants. Fungal attack is evaluated after incubation for 8 days at 22.degree. C. at 50% relative humidity to determine the protection given by the compound. b) After 1 weeks cultivation, wheat plants are infected with ascospores shaken from inoculum plants. After 24 hours, the wheat plants are sprayed with a spray mixture (200 ppm active ingredient/20% acetone/0.25% Triton X155). Fungal attack is evaluated after incubation for 8 days at 22.degree. C. at 50% relative humidity to determine the degree of curative activity provided by the compound. c) After 1 weeks cultivation, wheat plants are infected with ascospores shaken from inoculum plants. After 24 hours, the soil in which the wheat plants are growing is drenched with the drench mixture (200 ppm active ingredient/20% acetone/0.25% Triton X155). Fungal attack is evaluated after incubation for 8 days at 22.degree. C. at 50% relative humidity to determine the degree of curative activity provided by the compound. 2. Action against Puccinia recondita on wheat a) After 1 weeks cultivation, wheat plants sprayed to run off with a spray mixture (200 ppm active ingredient/20% acetone/0.25% Triton X155). After 2 hours, the treated plants are infected with a spore. Fungal attack is evaluated after incubation for 1 day at 95-100% relative humidity at 20.degree. C. followed by 7 days at 25.degree. C. at 50% relative humidity to determine the protection given by the compound. b) After 1 weeks cultivation, wheat plants are infected with a spore suspension After 24 hours, the infected plants are sprayed to run off with a spray mixture (200 ppm active ingredient/20% acetone/0.25% Triton X155. Fungal attack is evaluated after incubation for 1 day at 95-100% relative humidity at 20.degree. C. followed by 7 days at 25.degree. C. at 50% relative humidity to determine the degree of curative activity provided by the compound. c). After 1 weeks cultivation, wheat plants are infected with a spore suspension After 24 hours, the soil in which the wheat plants are growing was drenched with the drench mixture (200 ppm active ingredient/20% acetone/0.25% Triton X155). Fungal attack is evaluated after incubation for 1 day at 95-100% relative humidity at 20.degree. C. followed by 7 days at 25.degree. C. at 50% relative humidity to determine the degree of curative activity provided by the compound. Based on the spectrum of activity, the compounds of the present invention can be used to protect or cure plants of phytopathogenic fungi affecting various useful crops. The following species of plants are suitable for the use described in the scope of the invention of the stated compounds: cereal (e.g. wheat, rye, oat, barley, rice, sorghum and related crops); beet (sugar beet and fodder beet); pomes, dropes and soft fruit (e.g. apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries, and blackberries); leguminous plants (e.g. beans, peas, lentils and soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans and groundnuts); curbitats (e.g. cucumber, squash, and melon); fiber plants (e.g. cotton, flax, hemp, and jute); citrus fruit (e.g. oranges, lemons, madarins and grapefruit); vegetables (e.g. lettuce, cabbage, spinach, carrot, asparagus, paprika, onions, tomatoes, and potatoes); lauraceae: (avocados, cinnamon and camphor); or plants such as maize, tobacco, nuts, coffee, sugar cane, tea, vines, hops, bananas and natural rubber plants, as well as ornamentals (flowers, shrubs, broad-leaved trees and evergreens, such as conifers). However, the aforementioned plant species do not constitute a limiting list of plants with respect to spectrum by the stated compounds. The compounds of formula I are particularly useful for controlling the following plant diseases: Erysiphe graminis in cereals, Erysiphe cichoracearum and Sphaerotheca fuliginea in cucurbits, Podosphaera leucotricha in apples, Uncinula necator in vines, Puccinia species in cereals, Rhizoctonia solani in cotton, Ustilago species in cereals and sugar cane, Venturia inaequalis (scab) in apples, Helminthosporium species in cereals, Septoria nodorum in wheat, Botrytis cinerea (gray mold) in strawberries and grapes, Cercospora arachidicola in groundnuts, Pseudocercosporella herpotrichoides in wheat and barley, Pyricularia oryzae in rice, Phytophthora infestans in potatoes and tomatoes, Fusarium and Verticillium species in various plants, Plasmopara viticola in grapes, Altemaria species in fruit and vegetables. The compounds of formula I may also be used for protecting materials (e.g. preservation of timber against Paecilomyces variotii). Pharmaceutical Compositions. While it is possible that, for use in therapy, compounds of the invention may be administered as the raw chemical, it is preferable to present the active ingredient in a pharmaceutical composition. The invention thus further provides a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, together with one or more pharmaceutically acceptable carriers thereof and, optionally, other therapeutic and/or prophylactic ingredients. The carrier(s) must be `acceptable` in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof. The compositions of the invention include those in a form especially formulated for oral, buccal, parenteral, implant, rectal, topical, ophthalmic or genito-urinary administration or in a form suitable for administration by inhalation or insufflation. Tablets and capsules for oral administration may contain conventional excipients such as binding agents, for example, syrup, acacia, gelatin, sorbitol, tragacanth, mucilage of starch or polyvinylpyrrolidone; fillers, for example, lactose, sugar, microcrystalline cellulose, maize-starch, calcium phosphate or sorbitol; lubricants, for example, magnesium stearate, stearic acid, talc, polyethylene glycol or silica; disintegrants, for example, potato starch or sodium starch glycollate or crosscarmellose sodium; or wetting agents such as sodium lauryl sulphate. The tablets which include chewable, dispersible or effervescent tablets may be coated according to methods well known in the art. Oral liquid preparations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups or elixirs, or may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations may contain conventional additives such as suspending agents, for example, sorbitol syrup, methyl cellulose, glucose/sugar syrup, gelatin, hydroxyethylcellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenated edible fats; emulsifying agents, for example, lecithin, sorbitan mono-oleate or acacia; non-aqueous vehicles (which may include edible oils), for example, almond oil, fractionated coconut oil, oily esters, propylene glycol or ethyl alcohol; and preservatives, for example, methyl or propyl p-hydroxybenzoates or sorbic acid. For buccal administration the composition may take the form of tablets or lozenges formulated in conventional manner. The composition according to the invention may be formulated for parenteral administration by injection or continuous infusion. Formulations for injection may be presented in unit dose form in ampoules, or in multi-dose containers with an added preservative. The compositions may take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents. Alternatively the active ingredient may be in powder form for constitution with a suitable vehicle, e.g. sterile, pyrogen-free water, before use. For administration by inhalation the compositions according to the invention are conveniently delivered in the form of an aerosol spray presentation from pressurized packs with the use of a suitable propellant, e.g. dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas, or from a nebuliser. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Alternatively, for administration by inhalation the compositions according to the invention may take the form of a dry powder composition, for example a powder mix of the compound and a suitable powder base such as lactose or starch or as a modified physical form of the drug substance alone. The powder composition may be presented in unit dosage form in, for example, capsules or cartridges of e.g. gelatin, or blister packs from which the powder may be administered with the aid of an inhaler or insufflator. The compositions may take the form of a suppository, e.g. containing a conventional suppository base, or a pessary, e.g. containing a conventional pessary base. The compositions may also be formulated for topical administration in the form of ointments, creams, gels, lotions, shampoos, powders (including spray powders), pessaries, tampons, sprays, dips, aerosols, drops (e.g. eye, ear or nose drops) or pour-ons. Ointments and creams may, for example, be formulated with an aqueous or oily base with the addition of suitable thickening and/or gelling agents. Ointments for administration to the eye may be manufactured in a sterile manner using sterilized components. Pour-ons may, for example, be formulated for veterinary use in oils containing organic solvents, optionally with formulatory agents, e.g. stabilizing and solubilizing agents. Pessaries and tampons for vaginal insertion may be formulated using conventional techniques and, where appropriate, may contain an effervescent vehicle. Such compositions may also contain other active ingredients such as corticosteroids, antibiotics or antiparasitics as appropriate. Liquid preparations for intranasal delivery may take the form of solutions or suspensions and may contain conventional excipients such as tonicity adjusting agents, for example, sodium chloride, dextrose or mannitol; preservatives, for example benzalkonium chloride, thiomersal, phenylethyl alcohol; and other formulating agents such as suspending, buffering, stabilizing, dispersing and or flavouring agents. Transdermal administration may be affected by the design of a suitable system which promotes absorption of the active compound through the skin and would typically consist of a base formulation enclosed within an adhesive stick-on patch comprising backing films, membranes and release liners. Such systems may include absorption enhancers such as alcohols or work by promoting ionotophoresis. The composition according to the invention may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. Thus, for example, a compound of the invention may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt. When the compositions comprise dosage units, each unit will preferably contain 0.001 mg to 1000 mg, advantageously 0.01 mg to 400 mg, of active ingredient where a compound of the invention is to be administered orally. The daily dosage as employed for adult human treatment will preferably range from 0.001 mg to 5000 mg of active ingredient, most preferably from 0.01 mg to 2000 mg which may be administered in 1 to 4 daily doses, for example, depending on the route of administration and on the condition of the patient and the disease to be treated. The compound may be administered by intravenous infusion using, for example, up to 50 mg/kg/day of the active ingredient. The duration of treatment will be dictated by the rate of response rather than by arbitrary number of days. Compounds of the invention may also be used in combination with other therapeutic agents, and the invention thus provides, in a further aspect, a combination comprising a compound of the invention together with another therapeutically active agent. Thus, for example the compounds of the invention may be used in combination with one or more other antifungal agents, such as a polyenic derivative e.g. (Amphotericin B, Nystatin, a lipid formulation of Amphotericin B) an azole derivative e.g. (Fluconazole, Intraconazole, Ketoconazole, Miconazole, Clotrimazole, ZD-08070, UK-109496, SCH 56592), 5-Fluorocytosine, a Pneumocandin or Echinocandin derivative such as Cilofungin, LY-303366, L-733560, L-743872 or other cell wall active compound such as Nikkomycin Z and/or one or more immunomodulating agents such as an interferon e.g. (IFN-), interleukine e.g. (IL-1, IL-2, IL-3 and IL-8) and colony stimulating factors, [(G)-CSF, (M)-CSF and (GM)-CSF] and defensines. Particularly advantageous compounds for use with compounds of the invention include Intraconazole, Flucytosine, Fluconazole or Amphotericin B. When the compounds of the invention are administered in combination with another antifungal agent the compounds of the invention and the other fungal agent can be administered at the recommended maximum clinical dosage or at lower doses. The combinations referred to above may conveniently be presented for use in the form of a pharmaceutical formulation and thus pharmaceutical formulations comprising a combination as defined above together with a pharmaceutically acceptable carrier thereof comprise a further aspect of the invention. The individual components of such combinations may be administered either sequentially or simultaneously in separate or combined pharmaceutical formulations When a compound of the invention is used in combination with a second therapeutic agent against the same condition the dose of each compound may differ from that when the compound is used alone. Appropriate doses will be readily appreciated by those skilled in the art. Agrochemical Compositions. The compounds of formula I can be used in either an unmodified form or preferably together with adjuvants conventionally employed in the art of agrochemical formulation and are for this purpose forms known mainly as: emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute solution, suspensions (including high-percentage aqueous, oily or other suspensions), dispersions, oil dispersions, broadcasting agents, wettable powders, soluble powders, dusts, granules, and encapsulations. The formulations are prepared in known manner, e.g. by homogeneously mixing and/or grinding the active ingredients with extenders, e.g. solvents, solid carriers and, where appropriate, surface-active compounds (surfactants). Powders, dusts and broadcasting agents may be prepared by mixing or grinding the active ingredients with a solid carrier. Granules, e.g., coated, impregnated or homogeneous granules, may be prepared by bonding the active ingredients to solid carriers. Suitable solvents are: aromatic hydrocarbons, preferably the fractions containing 8 to 12 carbon atoms, such as xylene mixtures or substituted naphthalenes, chlorinated aromatics such as chlorobenzenes, phthalates, such as dibutyl or dioctyl phthalate, aliphatic hydrocarbons, such as cyclohexane or paraffins, alcohols and glycols and their ethers and esters, such as ethanol, ethylene glycol, ethylene glycol monomethyl or monoethyl ether, ketones such as cyclohexanone, amines such as ethanolamine, strongly polar solvents, such as N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethylformamide, and vegetable oils or epoxidised vegetable oils, such as epoxidised coconut oil or soybean oil; and water. Examples of surfactants are: alkali metal, alkaline earth metal and ammonium salts of aromatic sulfonic acids, e.g., ligninsulfonic acid, phenolsulfonic acid, naphthalenesulfonic acid and dibutylnaphthalenesulfonic acid, and of fatty acids, alkyl and alkylaryl sulfonates, and alkyl, lauryl ether and fatty alcohol sulfates, and salts of sulfated hexadecanols, heptadecanols, and octadecanols, salts of fatty alcohol glycol ethers, condensation products of sulfonated naphthalene and naphthalene derivatives with formaldehyde, condensation products of naphthalene or naphthalenesulfonic acids with phenol and formnaldehyde, polyoxyethylene octylphenol ethers, ethoxylated isooctylphenol, ethoxylated octylphenol and ethoxylated nonylphenol, alkylphenol polyglycol ethers, tributylphenyl polyglycol ethers, alkylaryl polyether alcohols, isotridecyl alcohol, fatty alcohol ethylene oxide condensates, ethoxylated castor oil, polyoxyethylene alkyl ethers, ethoxylated polyoxypropylene, lauryl alcohol polyglycol ether acetal, sorbitol esters, lignin-sulfite waste liquors and methyl cellulose. Examples of solid carriers are mineral earths such as silicic acids, silica gels, silicates, talc, kaolin, attapulgus clay, limestone, lime, chalk, bole, loess, clay, dolomite, diatomaceous earth, aluminas calcium sulfate, magnesium sulfate, magnesium oxide, ground plastics, fertilizers such as ammonium sulfate, ammonium phosphate, ammonium nitrate, and ureas, and vegetable products such as grain meals, bark meal, wood meal, and nutshell meal, cellulosic powders, etc. Compounds of formula I may be mixed and applied together with other active ingredients, for example herbicides, insecticides, bactericides, nematocides, molluscicides, growth regulators, micronutrients, and fertilizers. The other ingredients may also be one or more fungicides belonging to but not restricted to the following classes of fungicides: carboxamides, benzimidazoles, triazoles, hydroxypyridines, dicarboxamides, phenylamides, thiadiazoles. carbamates, cyano-oximes, cinnamic acid derivatives, morpholines, imidazoles, B-methoxy acrylates and pyridines/pyrimidines. Furthermore, these additional active ingredients may be used as mixtures of several of the preparations, if desired together with other application promoting adjuvants usually used in the art of formulation. Suitable carriers and adjuvants can be solid or liquid and correspond to the substances typically used in formulation technology (e.g. natural or regenerated mineral substances, solvents, disperants, and wetting agents). The following list of fungicides with which compounds of formula I may be combined is intended to illustrate possible combinations but not to impose any restrictions. Examples of fungicides which may be combined with compounds of formula I are: sulfur, dithiocarbamates and their derivatives, such as ferric dimethyldithiocarbamate, zinc dimethyldithiocarbamate, zinc ethylenebisdithiocarbamate, manganese ethylenebisdithiocarbamate, manganese zinc ethylenediaminebisdithiocarbamate, tetramethylthiuram disulfides, ammonia complex of zinc N,N'-ethylenebisdithiocarbamate, ammonia complex of zinc N,N'-propylenebisdithiocarbamate, zinc N,N'-propylenebisdithiocarbamate and N,N'-polypropylenebis (thiocarbamyl) disulfide; nitro derivative, such as dinitro(1-methylheptyl)-phenyl crotonate, 2-sec-butyl-4,6-dinitrophenyl 3,3-dimethylacrylate,2-sec-butyl-4,6-dinitrophenyl isopropylcarbonate and diisopropyl 5-nitroisophthalate; heterocyclic substances, such as 2-heptadecylimidazol-2-yl acetate, 2,4-dichloro-6-(o-chloroanilino)-s-triazine, O,O-diethyl phthalimidophosphonothioate, 5-amino-1-[bis-(dimethylamino)-phosphinyl]-3-phenyl-1,2,4-triazole, 2,3-dicyano-1,4-dithioanthraquinone, 2-thio-1,3-dithio[4,5-b]quinoxaline, methyl 1-(butylcarbamyl)-2-benzimidazolecarbamate, 2-methoxycarbonylaminobenzimidazole, 2-(fur-2-yl)-benzimidazole, 2-(thiazol-4-yl)benzimidazole, N-(1,1,2,2-tetrachloroethylthio)tetrahydrophthalimide, N-trichloromethylthiotetrahydrophthalimide, N-trichloromethylthiophthalimide, N-dichlorofluoromethylthio-N',N'-dimethyl-N-phenylsulfuric acid diamide, 5-ethoxy-3-trichloromethyl-1,2,3-thiadiazole, 2-thiocyanatomethylthiobenzothiazole, 1,4-dichloro-2,5-dimethoxybenzene, 4-(2-chlorophenylhydrazono)-3-methyl-5-isoxazolone, 2-thiopyridine 1-oxide, 8-hydroxyquinoline and its copper salt, 2,3-dihydro-5-carboxanilido-6-methyl-1,4-oxathiyne, 2,3-dihydro-5-carboxanilido-6-methyl-1,4-oxathiyne 4,4-dioxide, 2-methyl-5,6-dihydro-4H-pyran-3-carboxanilide, 2-methylfuran-3-carboxanilide, 2,5-dimethylfuran-3-carboxanilide, 2,4,5-trimethylfuran-3-carboxanilide, 2,5-dimethyl-N-cyclohexylfuran-3-carboxamide, N-cyclohexyl-N-methoxy-2,5-diethylfuran-3-carboxamide, 2-methylbenzanilide, 2-iodobenzanilide, N-formyl-N-morpholine-2,2,2-trichloroethylacetal, piperazine-1,4-diylbis-(1-(2,2,2-trichloroethyl)-formamide), 1-(3,4-dichloroanilino)-1-formylamino-2,2,2-trichloroethane, 2,6-dimethyl-N-tridecylmorpholine and its salts, 2,6-dimethyl-N-cyclododecylmorpholine and its salts, N[3-(p-tert.-butylphenyl)-2-methylpropyl]-cis-2,6-dimethylmorpholine, N-3-(p-tert.-butylphenyl)-2-methylpropyl]-piperidine, 1-2-(2,4-dichlorophenyl)-4-ethyl-1,3-dioxolan-2-yl-ethyl]-1H-1,2,4-triazol e, 1-[2-(2,4-dichlorophenyl)-4-n-propyl-1,3-dioxolan-2-yl-ethyl]-1H-1,2,4-tri azole, N-(n-propyl)-N-(2,4,6-trichlorophenoxyethyl)-N]-imidazolylurea, 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)-butan-2-one, 1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)-butan-2-ol, alpha -(2-chlorophenyl)-alpha-(4-chlorophenyl)-5-pyrimidinemethanol, 5-butyl-(2-dimethylamino-4-hydroxy-6-methylpyrimidine, bis-(p-chlorophenyl)-3-pyridinemethanol, 1,2-bis-(3-ethoxycarbonyl-2-thioureido)-benzene, 1,2-bis-(3-methoxycarbonyl-2-thioureido)-benzene, and various fungicides, such as dodecylguanidine acetate, 3-[3-(3,5-dimethyl-2-oxycyclohexyl)-2-hydroxyethyl]-glutaramide, hexachlorobenzene, DL-methyl-N-(2,6-dimethylphehyl)-N-fur-2-yl alanate, methyl DL-N-(2,6-dimethylphenyl)-N-(2]-methoxyacetyl)-alanate, N-(2,6-dimethylphenyl)-N-chloroacetyl-DL-2-aminobutyrolactone, methyl DL-N-(2,6-dimethylphenyl)-N-(phenylacetyl)-alanate, 5-methyl-5-vinyl-3-(3,5-dichlorophenyl)-2,4-dioxo-1,3-oxazolidine, 3-[3,5-dichlorophenyl]-5-methyl-5-methoxymethyl-1,3-oxazolidine-2,4-dione, 3-(3,5-dichlorophenyl)-1-isopropylcarbamylhydantoin, N-(3,5-dichlorophenyl)-1,2-dimethylcyclopropane-1,2-dicarboximide, 2-cyano-[N-(ethylaminocarbonyl)-2-methoximino]-acetamide, 1-[2-(2,4-dichlorophenyl)-pentyl]-1H-1,2,4-triazole, 2,4-difluoro-a-(1H-1,2,4-triazol-1-ylmethyl)-benzhydryl alcohol, N-(3-chloro-2,6-dinitro-4-trifluoromethylphenyl)-5-trifluoromethyl-3-chlor o-2-aminopyridine, and 1-((bis-(4-fluorophenyl)-methylsilyl)-methyl)-1H-1,2,4-triazole. As with the nature of compositions, the method of application such as spraying, atomizing, dusting, scattering, coating, dressing, and pouring are chosen in accordance with the intended objectives of the application and the prevailing circumstances. One method of applying the active ingredient or agrochemical composition containing at least one of the stated compounds is application to the plants (i.e. foliar application). However, the active ingredient can also penetrate the plant through the roots via the soil (i.e. soil application). This may be in the form of either a liquid application to the soil (drench) or a granular application. The active ingredient can also be applied to plant propagation material such as seeds (fruits, tubers or grains) or plant cuttings, in either liquid form (coating) or in solid form (dressing). Seeds, for example, can be dressed before sowing. The compounds of the invention can also be applied to grains either by impregnating the grains with a liquid formulation of by coating them with a solid formulation. The composition can also be applied to the locus of planting when planting the propagation material, for example to the seed furrow during sowing. Advantageous rates of application are normally from 10 g to 50 kg of active ingredient (a.i.) per hectare, preferably 100 g to 2 kg a.i./ha, most preferably 100 g to 600 g a.i./ha. The active ingredients of the stated compounds are typically used in the form of compositions and can be applied to the plant, or to parts of the plant either simultaneously or in succession with further active ingredients. These further active ingredients can be fertilizers, additional micronutrients, or other plant growth affecting compounds. They can, however, also be selective herbicides, insecticides, bactericides, nematocides, insecticides, and molluscicides, as well as other fungicides. |
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