ANTIFUNGAL FUSACANDINS

Abstract: Novel antifungal agents having formula (I), wherein R is hydrogen or -C(O)-R1 wherein R1 is alkenyl, C2-C12-alkyl, aryl, arylalkenyl, arylalkyl, aryl-aryl-, arylalkoxy-aryl-, aryloxyl-aryl-, aryl-aryl-aryl- or arylalkoxy-aryl-aryl-, or pharmaceutically acceptable salts, esters or prodrugs thereof, as well as (i) pharmaceutical compositions comprising such compounds, (ii) methods of treatment using such compounds, and (iv) methods and fungal cultures useful in making the same.

Description: ANTTFUNGA FUSACANDINS This application is a continuation-in-part of U.S. Patent Application Serial No. 370,934, filed January 10, 1995, which is incorporated herein in its entirety, and hereafter is abandoned. Technical Field The present invention relates to novel fungal isolates of potential medicinal value as well as chemically modified derivatives thereof. More particularly, the invention relates to compounds isolated from cultures of the Fusarium genus, Fusarium sambucinum species, herein designated "fusacandins", as well as chemically modified derivatives thereof which possesses antifungal activity, as well as to methods and cultures of microorganisms useful for the preparation of fusacandins or fusacandin analogs, pharmaceutical compositions containing such compounds, and the use thereof in treating fungal infections. Background of the Invention The compounds of the present invention are related to those of the papulacandin class, described in J. Antibiotics 3_3(9):967-977 (1980). Papulacandins include BE-29602, disclosed in a published Japanese patent application of Banyu Pharmaceutical Co. (No. JP05170784- A, published July 9, 1993) and isolated from a Fusarium species of fungus, and chaetiacandin, disclosed in J. Antibiotics 28(4):455-459 (1985) and J. Antibiotics 38(4):544-546 (1985). The fusacandins are distinct from the papulacandin compounds, however, in that they contain three sugar moieties not previously described in connection with other members of this class. Summary of the Invention It has now been found that novel antifungal agents of the papulacandin class, herein designated "fusacandins", may be obtained by the fermentation of certain cultures belonging to the fungal strain Fusarium sp. AB 1900A-1314. Accordingly, in one aspect of the present invention are disclosed compounds of the formula: (I) as well as a pharmaceutically acceptable salt, ester of prodrug thereof. In the above formula (I), R is hydrogen or -C(O)-Rι wherein Ri is alkenyl, C2-C12- alkyl, aryl, arylalkenyl, arylalkyl, aryl-aryl-, arylalkoxy-aryl-, aryloxy-aryl, arylalkyl-aryl-, aryl-aryl-aryl- or arylalkoxy-aryl-aryl-, with the proviso that when aryl is naphthyl, alkoxy substutuents on naphthyl must have fewer than 8 carbon atoms; or a pharmaceutically acceptable acid, ester or prodrug thereof. Typical Ri groups are C2-Ci2-alkenyl groups containing one, two or three double bonds, C2-Ci2-alkyl, phenyl, naphthyl, anthracenyl, phenanthrenyl, biphenylenyl, styryl, benzyl, naphthylmethyl, biphenyl, naphthyl-phenyl-, phenyl-naphthyl-, benzyloxy-phenyl-, benzyloxy-naphthyl-, phenoxy-phenyl-, biphenyl-phenyl-, and benzyloxy-biphenyl. Preferred examples where Ri is alkenyl contain from four to twelve carbon atoms and two or three double bonds, especially about eight to ten carbon atoms and two or three double bonds. Examples where Ri is alkenyl having twelve or fewer carbon atoms and two or three double bonds are trans,cis-l,3-nonadienyl, trans,cis,trans-l,3,6-nonatrienyl, and trans.trans- 1,2-nonadienyl. In another aspect of the present invention are disclosed pharmaceutical compositions which comprise a compound of the invention in combination with a pharmaceutically acceptable carrier. In a further aspect of the invention is disclosed a method of suppressing or inhibiting a fungal infection in a patient in need of such treatment, comprising administering to the patient a therapeutically effective amount of a compound of the invention. In yet another aspect of the invention, a process for preparing the compounds of the invention is disclosed which comprises the steps of (a) culturing a microorganism having substantially all the characteristics of Fusarium sambu inum species AB 1900A-1314 under suitable conditions in a fermentation medium containing assimilable sources of carbon and nitrogen; (b) allowing the desired compound to accumulate in the fermentation medium; and (c) isolating the compound from the fermentation medium. Preferably, the microorganism to be cultured is Fusarium strain NRRL 21252 or a mutant or derivative thereof. Synthetic processes for preparing other compounds of the invention are described below. Similarly, in an additional aspect of the present invention is disclosed a biologically pure culture of a microorganism capable of producing the compounds of the invention, namely, a microorganism having substantially all the characteristics of Fusarium sambucinum species AB 1900A-1314. Preferably, the microorganism is Fusarium strain NRRL 21252 or a mutant or derivative thereof. Brief Description of the Drawings The present invention will be better understood in connection with the following figures, in which: FIGURE 1 is a proton nuclear magnetic resonance (NMR) spectrum of Fusacandin A in CD3OD; FIGURE 2 is a carbon NMR spectrum of Fusacandin A in CD3OD; FIGURE 3 is an infrared (IR) spectrum of Fusacandin A acquired in microscope mode; FIGURE 4 is a proton NMR spectrum of Fusacandin B in CD3OD; FIGURE 5 is a carbon NMR spectrum of Fusacandin B in CD3OD; FIGURE 6 is an IR spectrum of Fusacandin B acquired in microscope mode; FIGURE 7 is a proton NMR spectrum of Fusacandin C in CD3OD; FIGURE 8 is a carbon NMR spectrum of Fusacandin C in CD3OD; and FIGURE 9 is an IR spectrum of Fusacandin C acquired in microscope mode. Detailed Description of the Invention In one embodiment of the present invention, R is a radical of the formula: in which instance the compound is designated fusacandin A; In another embodiment of the present invention, R is hydrogen, in which instance the compound is designated fusacandin B; In yet another embodiment of the present invention, R is a radical of the formula: in which instance the compound is designated fusacandin C; A preferred embodiment of the present invention is a compound of Formula I: I wherein R is -C(O)-Rι where Ri is alkenyl, aryl, arylalkyl, aryl-phenyl-, arylalkoxy-phenyl-, aryloxy-phenyl, aryl-aryl-phenyl- or arylalkoxy-aryl-phenyl-; or a pharmaceutically acceptable acid, ester or prodrug thereof. A more preferred embodiment of the present invention is a compound of Formula I wherein R is -C(O)-Rι where Ri is an alkenyl groups containing 10 or fewer carbon atoms and two and three double bonds, phenyl, naphthyl, anthracenyl, phenanthrenyl, biphenylenyl, styryl, benzyl, naphthylmethyl, biphenyl, naphthyl-phenyl-, phenyl-naphthyl-, benzyloxy-phenyl-, benzyloxy-naphthyl-, phenoxy-phenyl-, biphenyl-phenyl-, or benzyloxy-biphenyl wherein phenyl or aryl groups are unsubstttuted or substituted with one or two groups selected from Ci-Cs-alkyl, allyloxy, Ci-Cg-alkoxy, methylenedioxy, and hydroxy. An even more preferred embodiment of the present invention is a compound of Formula I wherein R is -C(O)-Rι wherein Ri is phenanthrenyl, unsubstituted biphenyl or biphenyl substituted with Cι-C3-alkyl or Cι-C3-alkoxy. Preferred compounds are compounds of Formula I wherein R is selected from the group consisting of: More preferred compounds are compounds of Formula I wherein R is selected from the group consisting of: As used throughout this specification and in the appended claims, the following terms have the meanings specified: The term "biologically pure" as used herein refers to fungal cultures which are substantially free from biologically active contaminants. The terms "loweralkyl" or "alkyl" as used herein refer to straight or branched chain alkyl radicals containing from 1 to 20 carbon atoms, sometimes represented as C n -Crn-alkyl where n and m respectively represent the mininum and maximum number of carbon atoms in the alkyl radical. Examples of loweralkyl include, but are not limited to, methyl, ethyl, n- propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, n-pentyl, 1-methylbutyl, 2,2- dimethylbutyl, 2-methylpentyl, 2,2-dimethylpropyl, n-hexyl and the like. The term "alkylamino" as used herein refers to R^NH- wherein R is a loweralkyl group, for example, ethylamino, butylamino, and the like. The term "dialkylamino" as used herein refers to R RgN- wherein R7 and Rξ are independently selected from loweralkyl, for example diethylamino, methyl propylamino, and the like. The term "alkenyl" as used herein refers to a branched or straight hydrocarbon chain comprising two to twenty carbon atoms, preferably four to twelve carbon atoms, especially about eight to ten carbon atoms, which also comprises one or more carbon-carbon double bonds, preferably about one to three double bonds. The exact number of double bonds, in part, depends on the length of the alkenyl radical. Double bonds are typically separated by at least one single bond and exist in either a cis or trans configuration. Compounds of the invention may either have a known configuration or may exist as a mixture of isomers. Variations in these parameters, i.e., number of double bonds and cis or trans configuration, result in a wide variety of compounds, all of which are encompassed by the invention. Representative alkenyl groups include, but are not limited to, trans,cis-l,3-nonadienyl; trans,cis,trans-l,3,6-nonatrienyl; trans,trans-l,2-nonadienyl; 2-propenyl (i.e., allyl); 3-methyl- 2-butenyl; 3,7-dimethyl-2,6-octadienyl; 4,8-dimethyl-3,7-nonadienyl; 3,7,1 l-trimethyl-2,6, 10- dodecatrienyl and the like. The term "alkenyloxy" as used herein refers to a branched or straight hydrocarbon chain comprising two to twelve carbon atoms which also comprises one or more carbon-carbon double bonds which is linked to the parent molecular moiety through an oxygen atom. Representative alkenyloxy groups include 2-propenyloxy (i.e., allyl) and the like. The term "alkoxy" or "lower alkoxy" as used herein refers to R*O- wherein R* is a loweralkyl group, as defined above. Alkoxy may also be represented as C n -C m -alkoxy where n and m respectively represent the mininum and maximum number of carbon atoms in the alkoxy radical. Examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, n-butyloxy, tert-butoxy, and the like. The term "aryl" as used herein refers to a mono-, fused bicyclic or fused tricyclic carbocyclic ring system having one or more aromatic rings including, but not limited to, phenyl, naphthyl, tetrahydronaphthyl, phenanthrenyl, biphenylenyl, indanyl, indenyl and the like. The term "bicyclic aryl" as used herein includes naphthyl, tetrahydronaphthyl, indanyl, indenyl and the like. The term "tricyclic aryl" as used herein includes anthracenyl, phenanthrenyl, biphenylenyl, fluorenyl, and the like. Aryl groups (including bicyclic and tricyclic aryl groups) can be unsubstituted or substituted with one, two or three substituents independently selected from loweralkyl, haloalkyl, alkoxy, thioalkoxy, amino, alkylamino, dialkylamino, alkenyloxy, hydroxy, halo, mercapto, nitro, carboxaldehyde, carboxy, alkoxycarbonyl and carboxamide. Substituents also include methylenedioxy and ethylenedioxy. In addition, substituted aryl groups include tetrafluorophenyl and pentafluorophenyl. The term "aryl-aryl-" as used herein refers to two aryl groups which are the same or different linked by a covalent bond. Examples of aryl-aryl- include, but are not limited to, biphenyl, 4-(l-naphthyl)phenyl, 4-(2-naphthyI)phenyl, 4-phenylnaphth-l-yl and the like. The covalent linking bonds in aryl-aryl- are preferably para, i.e. 1,4-; and the preferred aryl-aryl- group is biphenyl. The term "aryloxy-aryl" as used herein refers to two aryl groups which are the same or different linked by an oxygen (-O-) atom. Examples of aryloxy-aryl include, but are not limited to, 4-phenoxyphenyl, 3-phenoxyphenyl, 4-phenoxy- 1 -naphthyl and the like. The term "aryl-aryl-aryl-" as used herein refers to three aryl groups which are the same or different linked to each other by covalent bonds. Examples of aryl-aryl-aryl- include, but are not limited to, 4-(biphenyl)phenyl, 4-(biphenyl)naphth-l-yl, 6-(biphenyl)naphth-2-yl and the like. The covalent linking bonds in aryl-aryl-aryl- are preferably para, i.e. 1 ,4-; and the preferred aryl-aryl-aryl- group is 4-(biphenyl)phenyl. The term "arylalkyl" as used herein refers to an aryl group as previously defined, appended to a loweralkyl radical, for example, benzyl and the like. The term "arylalkenyl" as used herein refers to an aryl group as previously defined, appended to a lower alkenyl radical, for example, cinnamyl and the like. The term "arylalkoxy" as used herein refers to an aryl group as previously defined, appended to a lower alkoxy radical, for example, benzyloxy, 1-naphthylmethoxy and the like. The term "fusacandin" as used herein refers to a nucleus of structure For example, 6'-propionyl fusacandin would have a CH3CH2C(O)- functionality attached at the site of substitution indicated above. The term "hydroxy-protecting group" or "O-protecting group" as used herein refers to a removable substituent which protects hydroxyl groups against undesirable reactions during synthetic procedures such as those O-protecting groups disclosed in T.H. Greene and P.G.M. Wuts, "Protective Groups in Organic Synthesis", 2nd edition, John Wiley & Sons, New York (1991), which is incorporated herein by reference. O-protecting groups comprise substituted methyl ethers, for example, methoxymethyl, benzyloxymethyl, 2-methoxyethoxymethyl, 2- (trimethylsilyl)ethoxymethyl, t-butyl, benzyl and triphenylmethyl; tetrahydropyranyl ethers; substituted ethyl ethers, for example, 2,2,2-trichloroethyl; silyl ethers, for example, trimethylsilyl, triethylsilyl, t-butyldimethylsilyl and t-butyldiphenylsilyl; and esters prepared by reacting the hydroxyl group with a carboxylic acid, for example, acetate, propionate, benzoate and the like. The term "hydroxy-protecting reagent" as used herein refers to those reagents which react with the hydroxy functionality to give the hydroxy protecting groups described above. For example, the hydroxy-protecting reagent triethylsilyl triflate affords the triethylsilyl hydroxy-protecting group. These reagents are described in Greene and Wuts, "Protective Groups In Organic Synthesis," 2nd edition, John Wiley & Sons, New York (1991). The term "mutant or derivative" as used herein refers to fungal strains which are obtained by mutagenization or genetic modification of- Fusarium sambucinum strain NRRL 21252 by techniques readily known in the art. The term "pharmaceutically acceptable salts, esters, and prodrugs" as used herein refers to those carboxylate salts, esters, and prodrugs of the compound of the present invention which are, within the scope of sound medical judgement, suitable for use in contact with with the tissues of humans and lower animals with undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit risk ratio, and effective for their intended use, as well as the zwitterionic forms, where possible, of the compounds of the invention. Pharmaceutically acceptable salts are well known in the art and refer to the relatively non-toxic, inorganic and organic acid addition salts of the compound of the present invention. . For example, S. M. Berge, et al. describe pharmaceutically acceptable salts in detail in Pharmaceutical Sciences. 66: 1-19 (1977) which is incorporated herein by reference. The salts can be prepared in situ during the final isolation and purification of the compounds of the invention, or separately by reacting the free base function with a suitable organic acid. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, loweralkyl sulfonate and aryl sulfonate. Examples of pharmaceutically acceptable, non-toxic esters of the compounds of this invention include Ci to alkanoyl esters wherein the alkanoyl group is a straight or branched chain. Esters of the compounds of the present invention may be prepared according to conventional methods. The term "pharmaceutically acceptable prodrugs" as used herein refers to those prodrugs of the compounds of the present invention which are, within the scope of sound medical judgement, suitable for use in contact with with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit risk ratio, and effective for their intended use, as well as the zwitterionic forms, where possible, of the compounds of the invention. The term "prodrug" refers to compounds that are rapidly transformed in vivo to yield the parent compound of the above formula, for example by hydrolysis in blood. A thorough discussion is provided in T. Higuch and V. Stella, Pro-drugs as Novel Delivery Systems. Vol. 14 of the A.C.S. Symposium Series, and in Edward B. Roche, ed., Bioreversible Carriers in Drug Design. American Pharmaceutical Association and Pergamon Press, 1987, both of which are incorporated herein by reference. Where appropriate, prodrugs of derivatives of compounds of the present invention may be prepared by any suitable method. For those compounds in which the prodrug moiety is an amino acid or peptide functionality, the condensation of the amino group with amino acids and peptides may be effected in accordance with conventional condensation methods such as the azide method, the mixed acid anhydride method, the DCC (dicyclohexyl-carbodϋmide) method, the active ester method (p-nitrophenyl ester method, N-hydroxy-succinic acid imide ester method, cyanomethyl ester method and the like), the Woodward reagent K method, the DCC- HOBT (1-hydroxy-benzotriazole) method and the like. Classical methods for amino acid condensation reactions are described in M. Bodansky, Y.S. Klausner and M.A. Ondetti, Peptide Synthesis. Second Edition, NY, 1976, which is incorporated herein by reference. Asymmetric centers may exist in the compounds of the present invention. Cis and trans isomers may also exist in the compounds of the present invention. Except where otherwise noted, the present invention contemplates the various stereoisomers, cis and trans isomers and mixtures thereof. The compounds of the invention exhibit in vitro activity as antifungal agents against a variety of fungal organisms and inhibit (l,3)-β-glucan synthetase. They are therefore expected to be useful in the treatment of fungal infections in mammals. When used in such treatment, a therapeutically effective amount of the compound of the present invention may be employed in pure form or, where such forms exist, in pharmaceutically acceptable salt, ester or prodrug form. Alternatively, the compound may be administered as pharmaceutical compositions containing the compound of interest in combination with one or more pharmaceutically acceptable excipients. By a "therapeutically effective amount" of the compound of the invention is meant a sufficient amount of the compound to treat the targeted disorder, at a reasonable benefit risk ratio applicable to any medical treatment, hich is administered in such quantities and over such a period of time as is necessary to obtain the desired therapeutic effect. It will be understood, however, that the total daily usage of the compounds and compositions of the present invention will be decided by the attending physician within the scope of sound medical judgement. The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed; and like factors well known in the medical arts. For example, it is well within the skill of the art to start doses of the compound at levels lower than required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. The total daily dose of the compound of this invention administered to a human or lower animal may range from about 0.1 to about 100 mg/kg/day or for topical administration from about 0.1 to about 10% in cream, ointment or other topical formulation or for rectal or vaginal administration from about 10 to about 500 mg per dose in a suitable vehicle. For purposes of oral administration, doses may be in the range of from about 1 to about 100 mg/kg/day or, more preferably, of from about 10 to about 20 mg/kg/day. If desired, the effective daily dose may be divided into multiple doses for purposes of administration; consequently, single dose compositions may contain such amounts or submultiples thereof as make up the daily dose. The pharmaceutical compositions of the present invention comprise a compound of the invention and a pharmaceutically acceptable carrier or excipient, which may be administered orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneally, topically (as by powders, ointments, or drops), bucally, or as an oral or nasal spray. By "pharmaceutically acceptable carrier" is meant a non-toxic solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. The term "parenteral" as used herein refers to modes of administration which include intravenous, intramuscular, intraperitoneal, intrasternal, subcutaneous and intraarticular injection and infusion. Pharmaceutical compositions of this invention for parenteral injection include pharmaceutically acceptable sterile nonaqueous solutions or aqueous dispersions, suspensions or emulsions as well as sterile powders for reconstitution into sterile injectable solutions or dispersions just prior to use. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), carboxymethylceljulose and suitable mixtures thereof, vegetable oils (such as olive oil), and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of coating materials such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants. These compositions may also contain adjuvants such as preservative, wetting agents, emulsifying agents, and dispersing agents. Prevention of the action of microorganisms may be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents such as sugars, sodium chloride, and the like. Prolonged absorption of the injectable pharmaceutical form may be brought about by the inclusion of agents which delay absorption such as aluminum monostearate and gelatin. In some cases, in order to prolong the effect of the drug, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides) Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions which are compatible with body tissues. The injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium just prior to use. Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates and sodium carbonate, e) solution retarding agents such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols and sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard- filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. The active compounds can also be in micro-encapsulated form with one or more excipients as noted above. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings and other coatings well known in the pharmaceutical formulating art. In such solid dosage forms the active compound may be admixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, e.g., tableting lubricants and other tableting aids such a magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes. The active compounds can also be in micro-encapsulated form, if appropriate, with one or more of the above-mentioned excipients. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethyl formamide, oils (in particular, cottonseed, groundnut, corn, olive, castor and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, and sweetening, flavoring and perfuming agents. Suspensions, in addition to the active compounds, may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, " bentonite, agar-agar, and tragacanth, and mixtures thereof. Topical administration includes administration to the skin or mucosa, including surface of the lung and eye. Compositions for topical administration, including those for inhalation, may be prepared as a dry powder which may be pressurized or non-pressurized. In non- pressurized powder compositions, the active ingredient in finely divided form may be used in admixture with a larger-sized pharmaceutically acceptable inert carrier comprising particles having a size, for example, of up to 100 micrometers in diameter. Suitable inert carriers include sugars such as lactose. Desirably, at least 95% by weight of the particles of the active ingredient have an effective particle size in the range of 0.01 to 10 micrometers. Dosage forms for topical or transdermal administration of a compound of this invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. The active component is admixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives or buffers as may be required. Ophthalmic formulation, ear drops, eye ointments, powders and solutions are also contemplated as being within the scope of this invention. Alternatively, the composition may be pressurized and contain a compressed gas, such as nitrogen or a liquified gas propellanL The liquified propellant medium and indeed the total composition is preferably such that the active ingredient does not dissolve therein to any substantial extent. The pressurized composition may also contain a surface active agent. The surface active agent may be a liquid or solid non-ionic surface active agent or may be a solid anionic surface active agent It is preferred to use the solid anionic surface active agent in the form of a sodium salt. Compositions for rectal or vaginal administration are preferably suppositories which can be prepared by mixing the compounds of this invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at room temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound. The compound of the present invention can also be administered in the form of liposomes. As is known in the art, liposomes are generally derived from phospholipids or other lipid substances. Liposomes are formed by mono- or multi-lamellar hydrated liquid crystals that are dispersed in an aqueous medium. Any non-toxic, physiologically acceptable and metabolizable lipid capable of forming liposomes can be used. The present compositions in liposome form can contain, in addition to a compound of the present invention, stabilizers, preservatives, excipients, and the like. The preferred lipids are the phospholipids and the phosphatidyl cholines (lecithins), both natural and synthetic. Methods to form liposomes are known in the art See, for example, Prescott. Ed.. Methods in Cell Biolopy. Volume. XTV, Academic Press, New York, N.Y., 1976, p. 33 etseq. The compounds of the present invention may be produced by culturing, in appropriate media, fungal microorganisms which are capable of producing fusacandins. The compounds are produced when the culture is grown in a stationary fermentation with a culture medium containing a source of carbon and a source of nitrogen. Media which are useful include an assimilable source of carbon such as starch, sugar, molasses, glycerol, a combination of glucose plus molasses, etc.; an assimilable source of nitrogen such as protein, protein hydrolysate, polypeptides, amino acids, peptone plus yeast extract or whole yeast, etc.; and other optional organic and inorganic ingredients which can be added to stimulate production of the fusacandin compounds. For example, inorganic anions and cations including potassium, magnesium, calcium, ammonium, sulfate, carbonate, phosphate, chloride, etc. may be added to the medium. Further, buffers such as calcium carbonate can be added to aid in controlling the pH of the fermentation medium. The stationary fermentation may include a solid support to increase the surface area available for fungal growth. Suitable supports include Shredded Wheat Spoon Size ® , rolled oats, barley, cracked co , rice, millet corn bran, wheat bran, oat bran, vermiculite, etc. The culture may be incubated in stationary vessel (without movement) or in a cylindrical or other vessel which is rolled or agitated to increase aeration. Other culture methods, such as a liquid, submerged, agitated culture process are feasible. In these cases, aeration may be provided by forcing sterile air through the fermentation medium. Agitation can be provided by shaking the container or by stirring the culture, for example, with a mechanical stirrer. The fermentation is generally carried out in a temperature range of from about 15 °C to about 35 °C. The pH of the fermentation is preferably maintained between 3 and 9. The compound is produced and accumulated between 3 and 28 days after inoculation of the fermentation medium. Subsequent to the fermentation process, the fusacandin compounds can be extracted from the fermentation broth as for example with ethyl acetate/acetone solvent mixtures. Partial purification of the active components can be achieved by sequential trituration of the organic extract with organic solvents such as ethyl acetate, ethanol and methanol in order to selectively remove the desired organic compounds. The extracts may be further purified by use of various partitioning solvent systems such as, for example, chloroform/methanol/water, hexane/ethyl acetate/methanol/water, or ethanol ethyl acetate water. Further purification and separation of individual components can be achieved by countercurrent chromatography in solvent systems such as, for example, ethyl acetate ethanol/water, chloroform/methanol water, or chloroform/carbon tetrachloride methanol/water, and/or by adsorption onto silica gel and subsequent elution with organic solvents and solvent mixtures such as ethyl acetate, chloroform and methanol. Size exclusion chromatography on resin such as SEPHADEX® LH-20, developed in a solvent such as methanol, affords the pure compound. In yet another aspect of the present invention are disclosed processes useful in the preparation of the above compounds represented in Schemes I and II. In Scheme I, fusacandin A (1) is treated with an hydroxy protecting reagent (for example, triethylsilyl triflate or trimethylsilyl triflate or triethylsilyl chloride or trimethylsilyl chloride) to give the protected fusacandin derivative 2 (wherein R' is an hydroxy protecting group). Reduction of the ester functionality (for example, using a reducing reagent such as dϋsobutyl aluminum hydride or lithium aluminum hydride or selectrides and the like) at the 6'- position of compound 2 affords the 6'-alcohol compound 3. The hydroxymethyl functionality is acylated (for example, using an acid chloride or an acid anhydride) to give the 6 -acyl compound 4 (wherein R is as defined above herein). Alternatively, the hydroxymethyl functionality may be reacted with a carboxylic acid compound in the presence of 4- dimethylaminopyridine and a coupling reagent such as dicyclohexylcarbodiimide to give compound 4. The acid chlorides, anhydrides and carboxylic acids (Rι-C(O)-Cl, Rι-C(O)-O-C(O)-Rι and R1-CO2H respectively) are either commercially available or readily prepared using organic synthesis methods known in the art The hydroxy protecting groups are removed (for example, using HF in acetonitrile or tetrabutylammonium fluoride in THF or acetic acid and the like) to give the desired compound 5. In a preferred embodiment shown in Scheme II, fusacandin A (i) is treated with triethylsilyl (TES) triflate in collidine to give the TES-protected fusacandin derivative (6). Reduction of the ester functionality using diisobutyl aluminum hydride affords the 6'- hydroxymethyl compound (7). The hydroxymethyl functionality is acylated (for example, using an acid chloride or an acid anhydride) to give compound £. The hydroxy protecting groups are removed (for example, using HF in acetonitrile or tetrabutylammonium fluoride in THF) to give the desired compound 9. Scheme I Scheme I cont. Scheme II Scheme II cont. The compounds, processes and uses of the present invention will be better understood in connection with the following examples, which are intended as an illustration of and not a limitation upon the scope of the invention. The following abbreviations were used: EtOAc for ethyl acetate, EtOH for ethanol, MeOH for methanol, THF for tetrahydrofuran and TLC for thin layer chromatography. Example 1 Identification and Characterization of of the Fusacandin-Producing Strain Fusarium SP. Strain AB 1900A-1314 The compounds of the present invention, "fusacandins", were first obtained from a fungus isolated from a conk (fruiting body of wood-attacking fungus) collected in Piatt County, Illinois. The culture, which was designated strain AB 1900A-1314, is a Fusarium species as indicated by the production of characteristic macroconidia. A subculture of this microorganism was deposited in the permanent collection of the National Center for Agricultural Utilization Research, United States Department of Agriculture, 1815 North University Street, Peoria, Illinois 61604, U.S.A., under the terms of the Budapest Treaty, and accorded accession number NRRL 21252. Strain AB 1900A-1314 was examined at the Pennsylvania State University, Fusarium Research Center, and identified as a strain of Fusarium sambucinum. The morphological and cultural characteristics of this strain grown on two media at 25 °C for seven days were as described below. The colors and numbers shown in parenthesis were assigned based on the Inter-Society Color Council-National Bureau of Standards (ISCC-NBS) Centroid Color Charts, U.S. Dept of Commerce supplement to NBS Cir. 553, Washington D.C., 1976. Colonies of strain AB 1900A-1314 on Potato Dextrose agar (Difco) were dense, floccose, medium yellow-pink (29), grew rapidly to 75-80 mm in diameter and produced a clear exudate. Aerial mycelium was pale pink in color (7) and the reverse was light orange (52) to medium orange (53). Spore structures were not found on this medium at seven days. As the culture aged, many raised, round, light orange (52) structures, 1-3 mm in diameter, developed on the agar surface. These aggregates were hard but could be broken apart by moderate pressure with an inoculating loop. Fragments of the structures under light microscopy consisted of flattened, irregular cells mixed with a few strands of mycelia. The aggregates appear to be similar to the perithecia-bearing stromata which Fusarium sambucinum (Gibberella pulicaris) can form on woody host tissue ( Booth, C: The Genus Fusarium. pp. 168-172, Commonwealth Mycological Institute, Kew, Surrey, England, 1971). Perithecia or asci, however, were not observed. Colonies grew rapidly on Cornmeal agar (Qifco) and attained a diameter of 75-80 mm in seven days. The culture produced characteristic four to six septate, sickle-shaped macroconidia and one to two septate microconidia on this medium. The colonies had white (263), wispy aerial mycelia and the reverse was colorless. Macroconidia were produced abundantly, measuring 37.5-70 x 5-7 μm while microconidia measured 20-37.5 x 3.75-7.5 μm. The culture developed medium orange (53) sporodochia after 14 days incubation on Commeal agar. Example 2 Growth of Fusarium Sp. Strain AB 1900A-1314 in Stationary Culture The fusacandin-producing culture, Fusarium sp. AB 1900A-1314, was maintained as a frozen inoculum stock by freezing a portion of the original inoculum and storing at -70 °C. The medium (Table 1) was used for seed growth and the medium (Table 2) was used for stationary fermentations. Table 1 Seed Medium Ingredients grams/liter Com steep powder (Roquette Corp., Gurnee, IL) 2.5 Glucose monohydrate 10.0 Oat flour (National Oats Co., Cedar Rapids, IA) 10.0 Tomato paste (made by Contadina Foods, Inc. Los 40.0 Angeles, CA) CaCl 2 * 2H 2 O 10.0 Trace element solution 10 mL/L Distilled water was added to achieve a volume of 1 liter. The pH was adjusted to pH 6.8. Reference: Goetz et al., J. of Antibiotics 38 : 1633- 1637 ( 1985). Trace Element Solution Ingredients grams/liter FeSO - 7H 2 O 1.0 MnCl 2 * 4H 2 O 1.0 CuCl 2 • 2H 2 O 0.025 CaCl 2 - 2H 2 O 0.1 H3BO3 0.56 (NH 4 ) 6 MoO 2 ' 4H 2 O 0.019 ZnSO • 7H 2 O 0.2 Distilled water was added to achieve a volume of 1 liter. Table 2 Fermentation Medium Distilled water was added to achieve a volume of 1 liter; the pH was not adjusted. Shredded Wheat Spoon Size® (Nabisco® Brands, Inc., East Hanover, NJ) was used as solid growth support, following separate sterilization. The seed flasks were prepared by dispensing 100 mL of the seed medium (Table 1) into 500 mL Erlenmeyer flasks. The flasks were sterilized for 30 minutes at 121 °C, 15 psi. Inoculum for the fermentation was prepared by inoculating 1% of the frozen inoculum into each of several seed flasks. The seed flasks were incubated for 72 hours at 28 °C on a rotary shaker, operated at 225 rpm, with a stroke of 2 inches (approximately 5 cm). The fermentation was conducted in 3 glass 20-liter carboys. Each carboy, containing 300 grams of Shredded Wheat Spoon Size ® was sterilized for 45 minutes at 121 °C, 15 psi. The fermentation medium was sterilized in 3 batches of 360 mL in 2-liter Erlenmeyer flasks. Sterilization was at 121 °C, 15 psi. The 360 mL of liquid medium was inoculated with 60 mL of 72 hour seed growth. The combination was mixed and added aseptically to a carboy containing 300 grams of Shredded Wheat Spoon Size ® . The mixture was again thoroughly mixed to distribute the inoculum. The carboys were incubated in an upright position at 20 °C for 21 days. Three carboys were prepared in this manner. Example 3 Growth of Fusarium Sp. Strain AB 1900A-1314 in Submerged Culture The seed flasks were prepared by dispensing 600 mL of the seed medium (Table 3) into 2-liter Erlenmeyer flasks. The flasks were sterilized for 30 minutes at 121 °C, 15 psi. Inoculum for the fermentation was prepared by inoculating 1% of the frozen inoculum into each of 3 seed flasks. The seed flasks were incubated for 72 hours at 28 °C on a rotary shaker, operated at 225 φm, with a stroke of 2 inches (approximately 5 cm). Thirty titers of production medium (Table 4) were prepared in a 42-liter, stainless steel, stirred fermentor (LH Fermentation) and sterilized at 121 °C and 15 psi for 1 hour. The antifoam agent XFO-371 (Ivanhoe Chemical Co,. Mundelein, IL) was added initially at 0.01%, and then as needed. The fermentor was inoculated with 1500 mL of the seed flask growth. The temperature was controlled at 28 °C. The agitation rate was 250 rpm and aeration was 1.5 vol vol/min. The head pressure was maintained at 5 psi. The fermentation was terminated at seven days, with a harvest volume of about 13 liters. Reference: Traxler et al., J. Antibiotics 30:289-296 (1977). Table 4 Submerged fermentation medium Distilled water was added to achieve a volume of 1 liter; the pH was not adjusted. Reference: VanMiddlesworth et al., J. Antibiotics 44:45-51 (1991). Example 4 Isolation of Fusacandin A from Stationary Culture To 3 carboys containing stationary culture were added 3 liters of acetone. The resulting mixture was allowed to soak for 18 hours. This acetone extract was removed and an additional 6 liters of acetone added to the stationary culture, left to soak for 1 hour and removed. This procedure was repeated two additional times. The combined acetone extracts were concentrated to afford 29.7 grams of brown oil. This oil was triturated sequentially with 2 liters each of hexane, EtOAc, EtOH, MeOH and distilled water. The ethanol soluble material was concentrated to afford 400 mg of tan oil which was subjected to silica gel chromatography on 200 grams of VARJAN ® 40μ silica gel eluted sequentially with 500 mL each of EtOAc, 5% MeOH in EtOAc, 10% MeOH in EtOAc, 25% MeOH in EtOAc, 50% MeOH in EtOAc, and 100% MeOH. The material which eluted with 10% MeOH in EtOAc was concentrated to afford 130 mg of a pale oil which was subjected to countercurrent chromatography on an Ito multi-layered coil planet centrifuge in a solvent system of CHCl3/MeOH/H 2 O (1:1:1), lower layer stationary. Fractions of 5 mL each were collected from this countercurrent chromatography with a solvent front at fraction 19, and fractions 43-45 were combined to yield 3.0 mg of a clear oil. This oil was subjected to size exclusion chromatography on a SEPHADEX ® LH-20 resin column developed in MeOH. The active fractions from this column were combined and concentrated to yield 1 8 mg of pure fusacandin A. Example 5 Isolation of Fusacandin A from Submerged Fermentation 15 liters of whole culture broth were added to 8 liters of acetone and the mixture was agitated for 1 hour, after which 15 liters of EtOAc was added, the mixture was agitated and the upper layer was removed. An additional two 8-liter extractions were made, combined with the first and concentrated under reduced pressure to yield 15 grams of brown oil. This oil was triturated sequentially with 2 liters each of hexane, EtOAc and MeOH. The MeOH soluble material was concentrated in vacuo to yield 780 mg of brown oil which was subjected to silica gel chromatography on 500 grams of VARIAN® 40 μ silica gel eluting sequentially with 1 liter each of EtOAc, 2% MeOH in EtOAc, 5% MeOH in EtOAc, 10% MeOH in EtOAc, 20% MeOH in EtOAc, 50% MeOH in EtOAc and 100% MeOH. The material which eluted with 50% MeOH in EtOAc was subjected to size exclusion chromatography on a SEPHADEX® LH-20 resin column developed in MeOH. Active fractions from this column were combined to yield 160 mg of pure fusacandin A. Example 6 Phvsico-Chemical Characterization of Fusacandin A Fusacandin A was characterized using IR, UV, J H and 13 C NMR spectroscopy. The resulting infrared, proton and carbon spectra are shown in Figures 1, 2 and 3. Fusacandin A has a molecular weight of 1022 (C5iH7 4 O 2 ι) and is a clear oil. [α] D = +58° (c = 0.67, MeOH). TLC characterization on Merck silica gel plates: Rf = 0.00 in EtOAc, Rf = 0.71 in 1 : 1 MeOH-EtOAc, Rf = 0.52 in acetone, and Rf 0.40 in 3:2 CHCl3-MeOH. An ultraviolet spectrum of fusacandin A acquired in MeOH/0.01 M NaOH contained a band at λmax = 254 nm (ε = 35,000) and end absorption. An infrared spectrum of fusacandin A acquired in microscope mode contained bands at 3372, 2955, 2927, 2858, 1702, 1634, 1459, 1411, 1375, 1335, 1396, 1267, 1146, 1076, 1049, and 1003 cm-l. Example 7 Isolation of Fusacandin B from Submerged Fermentation To 4900 liters of whole broth were added 3350 liters of acetone and 3700 liters of ethyl acetate. The resulting mixture was agitated for approximately 12 hours after which time the upper layer was removed, concentrated under reduced pressure, and deposited onto 10 kg of silica gel. This was loaded onto the top of a 240 kg silica gel column developed sequentially with 300 liters of EtOAc 300 liters of 25% MeOH in EtOAc, 300 liter of 50% MeOH in EtOAc, 300 liters of 75% MeOH in EtOAc and finally 300 liters of MeOH. A portion (25 g) of the material which eluted with 25% MeOH in EtOAc w s partitioned between 3:1:2 EtOAc/EtOH/H 2 O, and the upper layer from this partition was concentrated under reduced pressure to an oily solid residue. This residue was subjected to size exclusion chromatography on a SEPHADEX ® LH-20 resin column developed in MeOH. The active fractions from this column were combined based upon their behavior on thin layer chromatograph to yield fusacandin A (2.65 g) and fusacandin B (62 mg). Example 8 Physico-Chemical Characterization of Fusacandin B Fusacandin B was characterized using IR, UV, *H and 13 C NMR spectroscopy. The resulting infrared, proton and carbon spectra are shown in Figures 4, 5 and 6. Fusacandin B has a molecular weight of 872 (C4iH_oO 2 o) and is a white solid. m.p. 42-45 °C. [α] D = +1° (c = 0.4, MeOH). TLC characterization on Merck silica gel plates: R f = 0.00 in EtOAc, R f = 0.60 in 1 : 1 MeOH/EtOAc, Rf = 0.46 in acetone and Rf = 0.19 in 3:2 CHCl3/MeOH. An ultraviolet spectrum of fusacandin B acquired in MeOH or MeOH/O.OlM HC1 contained a band at λ max = 263 nm (ε = 18,000), 231 (21,000) and end absorption. An ultraviolet spectrum of fusacandin B acquired in MeOH/0.01 M NaOH contained a band at λ m aχ = 256 nm (ε = 22,000), and end absorption. An infrared spectrum of fusacandin B acquired in microscope mode contained bands at: 3305, 3040, 3005, 2880, 2850, 1708, 1645, 1625, 1570, 1465, 1410, 1380, 1315, 1265, 1155, 1080 and 1055 cm-*. Example 9 Isolation of Fusacandin C from Submerged Fermentation Fermentation was carried out in a 7500 liter fermentor charged to 5000 liters. At harvest, 2500 liters of acetone were added and the mixture was agitated for 4 hours. Ethyl acetate (5000 liters) was added and gentle agitation was continued for an additional 4 hours. The mixture was allowed to settle and the upper layer was removed and stored at 4 °C for 16 hours. A tan precipitate (178 grams) formed and was collected. This precipitate was chromatographed in 20 batches over a Sephadex ® LH-20 column (6 liters packed column volume) developed in methanol. Fractions containing fusacandins A plus C were combined and concentrated to a pale glass. A portion of this material (4 grams) was subjected to preparative HPLC on a LiChroprep ® C-8 (15-25 μM) column in an isocratic solvent system composed of acetonitrile/water (44:56). Although baseline separation of fusacandins A and C was not achieved, peak shaving generated a sample (21 mg) of pure fusacandin C. Fusacandin C was characterized using IR, UV, and *H NMR spectroscopy. The resulting infrared, proton and carbon spectra are shown in Figures 7, 8 and 9. Fusacandin C has a molecular weight of 1020 (C5iH7_P 2 ι) and is a white amorphous solid. TLC characterization on Merck silica gel plates: Rf = 0.70 in 1: 1 MeOHL-EtOAc, Rf = 0.50 in acetone, and R f 0.40 in 3:2 CHC-3-MeOH. An ultraviolet spectrum of fusacandin C acquired in MeOH or MeOH/0.01 M HC1 contained a band at λma = 264 nm (ε = 35,000), 226 (ε = 28,000) and 211 (ε = 38,000). An ultraviolet spectrum of fusacandin C acquired in MeOH/0.01 M NaOH contained a band at λ max = 258 nm (ε = 39,000) and 224 (ε = 38,000). An infrared spectrum of fusacandin C acquired in microscope mode contained bands at 3390, 2955, 2875, 1705, 1622, 1456, 1335, 1305, 1265, 1 145, and 1075 cπr*. 1H NMR (CD 3 OD, 300 MHz) δ 4.78 (d. lH. J=9.5 Hz), 3.98 (dd, IH, J=9.5, 9.2 Hz), 5.16 (t, IH, J=9.2 Hz), 3.86 (dd, IH, J=9.6, 9.2 Hz), 3.71 (mult, IH), 4.04 (mult, 2H), 6.27 (d, IH, J=2.5 Hz), 6.41 (d, IH, J=2.5 Hz), 4.64 (d, IH, J=12.2 Hz), 4.53 (d, IH, J=12.2 Hz), 4.43 (d, IH, J=7.3 Hz), 3.71 (mult, IH), 3.68 (mult, IH), 3.79 (mult, IH), 3.68 (mult, IH), 4.22 (dd, IH, J=11.5, 5.9 Hz), 4.14 (mult IH), 4.51 (d, IH, J=7.7 Hz), 3.58 (mult, IH), 3.50 (dd, IH, J=9.9, 3.5 Hz), 3.82 (dd, IH, J=3.5, 0.9 Hz), 3.55 (mult, IH), 3.79 (mult, IH), 3.73 (mult, IH), 5.88 (d, IH, J=15.4 Hz), 7.26 (dd, IH, J=15.4, 10.8 Hz), 6.27 (mult, IH), 6.14 (mult, IH), 2.38 (mult, 2H), 4.14 (mult, IH), 5.55 (dd, IH, J=15.2, 6.6 Hz), 6.16 (dd, IH, J=15.2, 10.8 Hz), 6.01 (br dd, IH, J=15.2, 10.8 Hz), 5.67 (dt, IH, J=15.2, 7.0 Hz), 2.06 (mult, 2H), 1.38 (mult, IH), 1.29 (mult, 2H), 1.32 (mult, 2H), 0.89 (t, 3H, J=6.9 Hz), 5.99 (d, IH, J=15.6 Hz), 7.73 (ddd, IH, J=15.6, 11.7, 1.1 Hz), 6.21 (mult, IH), 5.87 (mult, IH), 3.07 (br t, 2H, J=7.7 Hz), 5.32 (dtt, IH, J=9.2, 7.1, 1.6 Hz), 5.45 (dtt, IH, J=9.2, 7.1, 1.6 Hz), 2.11 (mult, 2H), 0.97 (t, 3H, J=7.5 Hz). 13 C NMR (CD3OD) 6 78.4 (CH), 71.9 (CH), 79.1 (CH), 78.3 (CH), 81.8 (CH), 61.6 (CH2), 114.4 (Q), 158.6 (Q), 104.4 (CH), 159.3 (Q), 109.4 (CH), 143.1 (Q), 63.7 (CH2), 104.0 (CH), 81.9 (CH), 74.8 (CH), 70.1 (CH), 73.7 (CH), 64.8 (CH2), 106.9 (CH), 74.1 (CH), 74.7 (CH), 70.6 (CH), 77.1 (CH), 62.9 (CH2), 168.9 (Q), 121.6 (CH), 146.1 (CH), 131.9 (CH), 141.3 (CH), 42.2 (CH2), 72.6 (CH), 134.0 (CH), 132.1 (CH), 131.0 (CH), 136.1 (CH), 33.6 (CH2), 30.1 (CH2), 32.5 (CH2), 23.5 (CH2), 14.4 (CH3), 168.5 (Q), 122.1 (CH), 141.2 (CH), 127.3 (CH), 141.0 (CH), 27.4 (CH2), 126.5 (CH), 134.2 (CH), 21.5 (CH2), 14.6 (CH3). Example 10 General Procedures for the Preparation of 6'-Acyl Fusacandins (Examples 11-46) Example 10A Pertriethylsilylated Fusacandin A To fusacandin A (7 g, 6.85 mmol) dissolved in collidine (45 mL, 341 mmol) at -15 °C under a nitrogen atmosphere was added dropwise triethylsilyl triflate (40 mL, 177 mmol). The reaction was stirred at 0 °C for two hours and quenched by the addition of pH 7 phosphate buffer. The mixture was combined with chloroform, and the organic layer was separated, dried, and evaporated. The residue was purified by silica gel chromatography eluting with 96:4 hexane-ethyl acetate to give 13.1 g (80%) of the title compound. Example 10B Pertriethylsilylated Fusacandin B To the compound resulting from Example 10A (13.1 g, 5.48 mmol) dissolved in 150 mL of hexane was added 1 M diisobutyl aluminun hydride in hexane (11 mL, 11 mmol) dropwise at -78 °C. The reaction was stirred at -78 °C for ten minutes and quenched by the addition of methanol (10 mL). After several minutes, 3 mL of water was added, and the mixture was warmed to 25 °C, stirred for 1 hour and filtered. The organic layer was separated, dried, and evaporated. The residue was purified by silica gel chromatography eluting with 94:6 hexane-ethyl acetate to give 8.59 g (70%) of the title compound. Example 10C 6'-Acylpertriethylsilylated fusacandins To a solution of 1 equivalent of carboxylic acid (Ri-CC^H), oxalyl chloride (1.5 eq.), and methylene chloride (5 mL) was added dropwise dimethylformamide (1.5 eq.). The solution was stirred at room temperature for 30 minutes, and the solvent was evaporated in vacua to give the acid chloride. To the compound resulting from Example 10B (0.5 g, 0.22 mmol) dissolved in 5 mL of chloroform was added 4-dimethylaminopyridine (0.54 g, 4.46 mmol) followed by 0.66 mmol of the acid chloride (Rι-C(O)-Cl). The reaction was stirred at 25 °C for 1- 2 hours and quenched by the addition of pH 7 phosphate buffer. The organic layer was diluted with additional chloroform and separated, dried, and evaporated in vacua. The residue was purified by silica gel column chromatography eluting with 95:5 hexane-ethyl acetate to give the title compound. Example 10D Alternate Preparation of 6'-Acylpertriethylsilylated fusacandins A mixture of the compound resulting from Example 10B (0.5 g, 0.22 mmol), 0.66 mmol of the carboxylic acid (Ri-CC^H), 4-dimethylaminopyridine (14 mg, 0.11 mmol), dicyclohexylcarbodiimide (0.14 g, 0.66 mmol), and 5 mL of toluene was heated at 80 °C for 3 hours. The reaction was quenched by the addition of pH 7 phosphate buffer. The organic layer was diluted with ethyl acetate and separated, dried, and evaporated. The residue was purified by silica gel chromatography eluting with 95:5 hexane-ethyl acetate to give the title compound. Example 10E 6'-Acyl fusacandins To the compound resulting from either IOC or 10D (100 mg) dissolved in 1 mL of THF at 23 °C was added 5% HF in CH3CN (0.2 mL). After 1.5 hours, the mixture was concentrated to half volume and added dropwise into pH 7 phosphate buffer (200 mL). The precipitate was filtered, washed with water and purified by preparative TLC eluting with 64:35:1 CHCl3-MeOH-HOAc to give the final compound. Examples 11-46 6'-Acyl fusacandins The following compounds shown in Table 5 were prepared by the procedures described in Example 10 from pertriethylsilylated Fusacandin B and the corresponding acid chloride (Rl-C(O)-Cl) or carboxylic acid (Rι-CO 2 H). These acid chlorides and carboxylic acid were either commercially available or readily prepared using synthetic organic chemistry reactions known in the art to modify commercially available starting materials. The side chain precursors for Examples 12, 13, 14, 15, 16, 18, 19, 20, 21, 22, 28, 30, 31 and 36 were available from Aldrich®. The side chain precursor for Example 11 was prepared by the method described in Tetrahedron 37: 2091 (1981). The side chain precursors for Examples 25, 26 and 27 were prepared by the method of Zee-Cheng, et al., J. Het. Chem. 9: 805 ( 1972). Examples of procedures for preparing various side chains are described below. These general procedures may be applied to the preparation of analogous compounds. Example 17 A 3.5-Di-t-butylcinnamic acid To 1 g of 3,5-di-t-butylbenzoic acid dissolved in THF (10 mL) was added at 25 °C a solution of 1 M BH3 HF (4 mL), and the mixture was stirred at this temperature for 1.5 hours. The mixture was quenched with 1 N NaOH (4 mL) and extracted with ethyl acetate. The combined organic extracts were dried over sodium sulfate and evaporated to give 3,5-di-t- butylbenzyl alcohol as a clear oil which was used directly in the next step. To the crude alcohol from above was added MnO 2 and CHCI3 (20 mL). The mixture was stirred overnight at 25 °C and filtered, and the organic solvent was evaporated. The crude residue was purified by flash chromatography on silica gel eluting with 1:6 ethyl acetate-hexane to give 0.3 g of 3,5-di-t-butylbenzaldehyde as a white solid. A solution of 0.3 g of the aldehyde prepared above in THF (1 mL) was added to a solution of sodium triethylphosphonoacetate prepared * by combining triethylphosphonoacetate (0.37 g, 1.2 eq.) and NaH (0.1 g, 50% dispersion, 1.5 eq.) in THF (5 mL) at 0 °C. The mixture was stirred at 0 °C for 1 hour and then quenphed with saturated ammonium chloride and ethyl acetate. The aqueous layer was extracted twice with ethyl acetate. The combined organic extracts were dried over sodium sulfate and evaporated to give ethyl trαAW-3,5-di-t- butylcinnamate as a yellow oil used directly for the next step. The crude cinnamate was dissolved in ethanol (1 mL) and 1 N NaOH (3 mL) and heated at 80 °C for 4 hours. The mixture was cooled, acidified with 1 N HC1, and extracted twice with ethyl acetate. The combined organic extracts were dried over sodium sulfate and evaporated to give the 3,5-di-t-butylcinnamic acid of sufficient purity for the acylation reaction. Examples 23A and 24A 6-Alkoxy-2-naphthoic acid To 6-hydroxy-2-naphthoic acid (Lancaster®) was added methanol and several drops of concentrated HC1. This mixture was refluxed overnight, the solvent was evaporated, and the residue was dissolved in methylene chloride. The resulting solution was washed with saturated NaHCO3 solution, dried over sodium sulfate and evaporated to give crude methyl 6-hydroxy- 2-naphthoate of sufficient purity for the next step. To 0.2 g of the crude naphthoate prepared above dissolved in acetone (8 mL) was added potassium carbonate (0.4 g, 4 eq.) and 3 equivalents of the corresponding alkyl halide (e.g., allyl bromide or benzyl bromide), and the mixture was refluxed for 3 hours. After cooling to ambient temperature, the mixture was filtered. The solids were rinsed with methylene chloride, and the filtrate was evaporated to give methyl 6-alkoxy-2-naphthoate of sufficient purity for the next step. The ester from above was dissolved in methanol (10 mL) and 1 N NaOH (0.5 mL) and refluxed overnight The mixture was cooled to ambient temperature, and the methanol was evaporated. The aqueous residue was acidified with 1 N HC1 and the solids are filtered and rinsed with hexane to give after drying the 6-alkoxy-2-naphthoic acid of sufficient purity for the acylation reaction. Examples 29A. 33A. 34A.35A. 39A and 40A Arvl Substituted Benzoic Acids To tetrakis(triphenylphosphine)palladium(0) (58 mg, 0.05 eq.) dissolved in toluene (3 mL) was added a solution of the bromo ester (0.25 g, 1 eq. of either ethyl p- or m- bromobenzoate) in toluene ( 5 mL). The mixture was stirred for 10 minutes, then 2 M sodium carbonate (2.3 mL, 4.6 eq.) was added followed by a solution of the boronic acid ( 0.2 g, 1.1 eq.). These acids were prepared as per Suzuki, et al., J. Org. Chem. 58: 2201-2208 (1993) in ethanol (3 mL). The reaction was refluxed with vigorous stirring for 30 minutes. The black mixture was cooled to ambient temperature and poured into ether, and the organic layer was separated, dried over sodium sulfate, and evaporated to give 0.38 g of crude ester. The crude bi-aryl product was used directly for the next step. The crude ethyl arylbenzoate was dissolved in dioxane (5 mL) and 10% NaOH (4 mL) and heated at 80 °C for 5 hours. The dioxane was evaporated, and the aqueous mixture was acidified. The precipitated solids were filtered and rinsed with water and hexane to produce the arylbenzoic acid sufficiently pure for the acylation reaction. Examples 32A. 37A. 38A. 42A. 43A and 44A Alkoxy or Arylalkoxy Substituted Biphenyl Carboxylic Acids A solution of 4-(4-hydroxyphenyl)benzoic acid (5 g), methanol (120 mL), and concentrated sulfuric acid (0.5 mL) was heated at 70 °C for 15 hours. The solution was cooled to ambient temperature, water (120 mL) was added, and the precipitated white solid was filtered. The filtered solid was washed with water and methanol and dried to yield 5.2 g (97%) of the methyl 4-(4-hydroxyphenyl)benzoate. A suspension of hydroxyl ester from above (2.0 g), the appropriate alkyl halide or arylalkyl halide (2.5 eq.), potassium carbonate (4.0 g, 3 eq.), and acetone (5 mL) was heated at 70 °C in a sealed tube for 18 hours. Water (30 mL) was added to the mixture, and the resulting solid precipitate was filtered and washed with water and methanol. The filtered solid was suspended in chloroform and refiltered. The filtrate was evaporated in vacua to give the methyl 4-(4-alkoxy or arylalkoxyphenyl)benzoate. A solution of the alkylated methyl ester prepared above (9.0 mmol), 1 ,4-dioxane (20 mL), and 1 M sodium hydroxide (25 mL) was heated at reflux for 2 hours. The solution was cooled and acidified with 1 M HC1, and the precipitated white solid was filtered. The filtered solid was washed with water and methanol and dried to yield the acid in sufficient purity for the acylation reaction. Examples 41 A 4-(4-O-Triethylsilyloxyphenyl)benzoic Acid A solution of 4-(4-hydroxyphenyl)benzoic acid (0.5 g, 2.33 mmol), rriethylamine (3 mL, 21.5 mmol), triethylsilyl trifluoromethanesulfonate (2 mL, 8.8 mmol), and THF (20 mL) was stirred at room temperature for 10 minutes. The mixture was quenched with pH 7 phosphate buffer and extracted with chloroform. The organic layer was separated, dried, and evaporated. The residue was purified by silica gel chromatography eluting with 9:1 CHCI3- MeOH to give 0.42 g (55%) of 4-(4-O-triethylsilyloxyphenyl)benzoic acid for use in the acylation reaction. Table 5 Ex. No. Structure of R Diagnostic H NMR peaks in (Supplied as the acid chloride CD3OU or carboxylic acid and reacted δ by the procedures of Example IOC or 10D) 11 , IH), 7.25 (dd, IH), 2H), 2.19 (q, 2H), 2.07 12 - * r 2.35 (m, 2H) H 3 C^^ 1.65 (m, 2H) 0.99 (t, 3H) 13 (t, 6H), 1.31 (m, 14H) 14 (d, 2H), 7.61 (t, IH), 7.5 (t, H), 2.02 2H), 7.4 17 1 ! 7.75 (d, IH), 7.52 (s, IH), 7.46 (s, 2H), 7.55 (d, IH), 1.34 (s, 18H) 18 , 2H), 1.79 19 8.69 (s, IH), 8.1 (d, IH), 8.05 (d, IH), 7.98 (d, IH), 7.92 (d, IH), 7.61 (t, IH), 7.59 (t, IH) 20 8.36 (d, IH), 8.13 (d, IH), 7.7 (t, IH), 21 .8 (d, 2H), 7.6 (d, 2H), 2.7 (q, 2H), 22 .75 (m, 4H), 7.51-7.4 (m, 23 8.57 (d, IH), 8.03 (t IH), 7.92 (t, IH), 7.83 (t, IH), 7.3-7.2 (m, 3H), 5.48 (d, IH), 5.3 (d, IH) 24 H), 8.04 (m, IH), 7.98 7.93 (m, IH), 7.5 (d, (t, 3H), 7.38-7.3 (m, 25 8.91 (d, IH), 8.8 (d, IH), 8.7 (s, IH), 8.34 (d, 2H), 7.95 (d, IH) 7.9 (d, IH), 7.84 (d, IH), 7.74- 7.63 (m, 2H), 7.76 (t, IH), 7.65 ( , IH) 26 9.45 (s, IH), 8.82 (d, IH), 8.26 (d, IH), 8.04 (d, IH), 7.96 (d, IH), 7.91 (d, IH), 7.82 (d, IH), 7.76 (t, IH), 7.65 (t, IH) 27 , 8.84 (m, IH), 8.79 (s, IH), 8.08 (d, IH), 7.74 (m, 2H), 28 7.62 (d, IH), 7.25 (s, IH), 6.84- 6.8 (m, 2H), 6.8-6.75 (m, 3H) 29 8.21 (d, 2H), 8.18 (s, IH), 8.0- 7.92 (m, 4H), 7.88 (d, IH), 7.82 (d, IH), 7.53-7.5 (m, 2H) 30 8.18 (d, 2H), 7.8 (d, 2H), 7.7 (d, 2H), 7.46 (t, 2H), 7.39 (t, IH) 31 (d,2H), 7.4 (t, 2H), 7.25-7.2 3H), 7.08 (d, 2H), 7.01 (d, 32 8.15 (d,2H), 7.75 (d, 2H), 7.62 (d, 2H), 7.0 (d, 2H), 3.82 (s, 3H) 33 (d, 2H), 7.8-7.7 2H), 7.45 (t, 34 H), 8.10 (d, IH), 7.92 7.75 (dd, 4H), 7.65-7.60 7.45 (t, 2H), 7.35 (t, 35 {-000$ 8.19 (d, 2H), 7.85 (d, 2H), 7.75 (d, 2H), 7.69 (d, 2H), 7.61 (d, CH, 2H), 7.0 (d, 2H), 1.8 (m, 2H), 0.98 (t, 3H) 36 , 7.72 (d, 2H), 7.2 (s, , IH), 6.91 (d, IH), , 2H), 7.62 ), 7.39 (t, (d, 2H), , 2H), 7.61 1.35 (alkyl , 7.82 (t, IH), 7.4- , 7.02 7.57 8.14 (d, 2H), 7.74 (d, 2H), 7.62 o QrG* } (d, 2H), 7.0 (d, 2H), 1.8 (m, 2H), CH, 1.05 (t, 3H) 2H), 7.62 1.37 (d, 44 , 7.74 (d, 2H), 7.62 (d, 2H), 1.8 (m, 2H) , In Vitro Assay of Antifun al Activity Minimal inhibitory concentrations (MICs) were determined by an agar dilution metho d . The test compounds were serially diluted in MeOH and 0.2 mL portions were mixed with 20 mL of molten, cooled Sabouraud dextrose agar (Difco). Yeast cell inoculum was prepared by growing cultures on Sabouraud dextrose agar for 18 hours at 32 °C and suspending the cells in phosphate buffered saline. Filamentous fungi were grown under the same conditions for 4 days to obtain spores. The inoculum level for all cultures was adjusted to 10 4 cells using a Petroff-Hauser cell counter. The glutarimide antifungal compounds cycloheximide or amphotericin B were used as a control. Inoculated test plates were incubated at 32 °C and examined after 20 hours. The results, shown in Tables 6a, 6b and 6c, demonstrate that the compounds of the present invention possess significant antifungal activity. Table 6a In Vitro Antifungal Activity of Fusacandin A MIC (ug/mL Microorganism Fusacan in A Candida albicans CCH442 Candida albicans ATCC997 Candida albicans ATCC 623 Candida tropicalis NRRL-Y-1 Candida k r ATTC 288 Torulopsis glabrata ATCC 155 Saccharomyces cereviseae GS1-36 Aspergillus niger ATCC 164 Nocardia asteroides ATTC 9970 Streptococcus pyrogenes EES61 Streptococcus bovis A-5169 Staphylococcus aureus ATTC 6538p Table 6b In Vitro Antifungal Activity of Fusacandin B MIC (u /mL) Microorganism Fusacandin B Am ho Crypto coccus albidus ATCC 341 Saccharomyces cereviseae GSl-36 A spergillus niger ATCC 164 Candida albicans ATCC 102 Candida albicans 579a Candida albicans CCH 442 Candida albicans ATCC 382 Candida albicans ATCC 623 Candida tropicalis NRRL Y-l Candida kefyr ATCC 288 Torulopsis glabrata ATCC 155 Table 6c In Vitro Antifungal Activity of Fusacandins MIC (iig/mL) Ex. No. V 4 1.56 7 50 11 3.12 12 50 13 12.5 14 12.5 15 1.56 16 12.5 17 6.25 18 0.78 19 3.12 20 6.25 21 0.39 22 6.25 Candida albicans ATCC 10231 II Candida albicans 579a m Candida albicans CCH 442 IV Candida albicans ATCC 38247 V CandMa albicans ATCC 62376 In Vitro Assay of Antifungal Activity Minimal inhibitory concentrations (MICs) were determined by a broth dilution assay described by Frost, D., Brandt, K., Cugier, D., and Goldman, R. in J. Antibiotics 48: 306- 310 (1995) which is incorporated herein by reference. The final concentration of cells was 2 10 5 organisms/mL. The results, shown in Table 6d demonstrate that the compounds of the present invention possess significant antifungal activity. In Vitro Inhibition of (1.3 β-Glucan Synthase Activity The fungal cell wall serves as a protective barrier and is essential for viability in a hypotonic environment. (l,3)-β-Glucan is a component of the Candida albicans cell wall, and the enzyme that biosynthesizes this polymer, glucan synthase, is not present in higher eukaryotes. (Glucan synthase is an integral plasma membrane protein that catalyzes polymerization of uridine diphosphate-glucose (UDP-Glc) into β-glucan.) Accordingly, gluca synthase represents an ideal target for the development of antifungal agents. A microtiter screen was established to detect inhibitors of (l,3)-β-glucan formation in C. albicans cell free extracts. Microsomes isolated from mid-log phase grown yeast were incubated with [ 1 C]UDP-Glc, effectors and test compound (fusacandin A, Example 4). The formation of the water-insoluble β-glucan product was measured on a filter after removing the substrate with water washes. The IC50 for fusacandin A was shown to be 20.5 μg/mL compared to 3.6 μg/mL for papulacandin B. The minimum inhibitory concentration (MIC) for fusacandin was 0.5 μg/mL compared to 1.0 μg mL for papulacandin B. In Vitro Inhibition of fl )-β-Glucan Svnthase Activity The assay was conducted in a final volume of 100 μL of 2.0 mM UDP-[ I C]-Glc (0.625 mCi/mmol), 1 mM EDTA, 8% (v/v) glycerol, 20 μM GTPgS, 0.5% Brij-35(v/v) or 0.8% BSA, 80 mM Tris/HCI, pH 7.75, and microsomal enzyme preparation C. albicans CCH 442 (100 μg of protein). A detailed description of this assay is described by Frost, D., Brandt, K. Capobioanco, and Goldman, R., Microbiology 140: 2239-2246 (1994) which is incorporated herein by reference. The results are shown in Table 7. It is understood that the foregoing detailed description and accompanying examples are merely illustrative and are not to be taken as limitations upon the scope of the invention, which is defined solely by die appended claims and their equivalents. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art, and may be made without departing from the spirit and scope thereof.

Claims: What is claimed is: A compound having the formula wherein R is hydrogen or -C(O)-Rι wherein Rj is alkenyl, C2-Ci2-alkyl, aryl, arylalkenyl, arylalkyl, aryl-aryl-, arylalkoxy-aryl-, aryloxy-aryl, arylalkyl-aryl-, aryl-aryl-aryl- or arylalkoxy-aryl-aryl-, with the proviso that when aryl is naphthyl, alkoxy substutuents on naphthyl must have fewer than 8 carbon atoms; or a pharmaceutically acceptable acid, ester or prodrug thereof. 2. A compound according to Claim 1 wherein R is -C(O)-Rj wherein Ri is alkenyl, aryl, arylalkyl, aryl-phenyl-, arylalkoxy-phenyl-, aryloxy-phenyl, aryl-aryl-phenyl- arylalkoxy-aryl-phenyl-. 3. A compound according to Claim 1 wherein R is -C(O)-Rι where Ri is C2-C12 alkenyl groups containing up to three double bonds, C2-Ci2-alkyl, phenyl, naphthyl, anthracenyl, phenanthrenyl, biphenylenyl, styryl, benzyl, naphthylmethyl, biphenyl, naphthyl-phenyl-, phenyl-naphthyl-, benzyloxy-phenyl-, benzyloxy-naphthyl-, phenoxy-phenyl-, biphenyl-phenyl-, or benzyloxy-biphenyl wherein phenyl or aryl groups ar unsubstituted or substituted with one or two groups selected from Ci-Cs-alkyl, allyloxy, - C8-alkoxy, methylenedioxy, and hydroxy. 4. A compound according to Claim 3 wherein Rj is alkenyl containing from four to twelve carbon atoms and two or three double bonds. 5. A compound according to Claim 3 wherein Rj is alkenyl containing from eight to ten carbon atoms and two or three double bonds. 6. A compound according to Claim 5 wherein Ri is trans,cis-l,3-nonadienyl, trans,cis,trans-l,3,6-nonatrienyl, or trans, trans- 1, 2 -nonadienyl. 7. A compound according to Claim 1 wherein R is -C(O)-Rι wherein R j is phenanthrenyl, unsubstituted biphenyl or biphenyl substituted with Cι-C3-alkyI or -C3- alkoxy. 8. A compound according to Claim 1 wherein R is selected from the group consisting of : . A compound according to Claim 1 wherein R is selected from consisting of: the group 10. A pharmaceutical composition comprising a compound according to Claim 1 in combination with a pharmaceutically acceptable carrier. 11. A pharmaceutical composition comprising a compound according to Claim 2 in combination with a pharmaceutically acceptable carrier. 12. A pharmaceutical composition comprising a compound according to Claim 3 in combination with a pharmaceutically acceptable carrier. 13. A method of treating a fungal infection in a patient in need of such treatment, comprising administering to the patient a therapeutically effective amount of a compound according to Claim 1. 14. A method of treating a fungal infection in a patient in need of such treatment, comprising administering to the patient a therapeutically effective amount of a compound according to Claim 2. 15. A method of treating a fungal infection in a patient in need of such treatment, comprising administering to the patient a therapeutically effective amount of a compound according to Claim 3. 16. A process for preparing a compound according to Claim 1 , comprising the steps of (a) culturing a microorganism having substantially all the characteristics of Fusarium species AB 1900A-1314 under suitable conditions in a fermentation medium containing assimilable sources of carbon and nitrogen; (b) allowing the compound to accumulate in the fermentation medium; and (c) isolating the compound from the fermentation medium. 17. A process according to Claim 10 wherein the microorganism is Fusarium strain NRRL 21252 or a mutant or derivative thereof.

Inventors: ALDER LISA A, BURRES NEAL S, HOCHLOWSKI JILL E, JACKSON MARIANNA, KLEIN LARRY L, LARTEY PAUL A, MCALPINE JAMES B, YEUNG CLINTON, ALDER, LISA, A., BURRES, NEAL, S., HOCHLOWSKI, JILL, E., JACKSON, MARIANNA, KLEIN, LARRY, L., LARTEY, PAUL, A., MCALPINE, JAMES, B., YEUNG, CLINTON
Applicants: ABBOTT LAB, ABBOTT LABORATORIES
Application year: 1996
Main classification: C07H15
IPC codes: A01N43, A61K31, A61P31, C07H15, C07H17, C12P17, C12R1