BACKGROUND OF THE INVENTION Natural compounds containing lactone rings demonstrate a wide spectrum of antifungal activity, but are generally too expensive to be used regularly as agricultural fungicides.

It is accordingly an object of the present invention to provide lactones and related compounds which have plant fungus inhibiting activity against various parasitic fungi which attack crops. A further object of the invention is to provide such compounds which are more economical than natural antifungal lactones. Other objects of the invention will appear from the description which follows.

It has surprisingly been found by the present inventors that lactones derived from carboxylic acids having formula (I) as defined below, and the corresponding hydroxycarboxylic acids, possess an interesting spectrum of plant fungus inhibiting activity.

Other surprising aspects of the invention are that such or similar activity is also exhibited by the corresponding oxocarboxylic acids, and by derivatives of the carboxylic function in both hydroxy and oxo acids.

SUMMARY OF THE INVENTION The present invention accordingly provides in one aspect, a composition for combatting plant fungi, which comprises at least one compound having plant fungus inhibiting activity, said at least one compound being selected from carboxylic acids of the formulae : RX (CHY) nC02H (I) and RX (CHY) CONH-Z-CO2H (il) the corresponding lactones and functionai derivatives of the carboxylic acid group, where R is an unsubstituted or substituted aromatic nucleus, X is CHOH or CO, n is an integer selected from 2,3,4 and 5, m is 1 or 2, each Y is independently H, C, 4 alkyl, C1 4 alkoxy, OH, NH2, halogen, substituted OH or substituted NH2, and Z is the residue of an a-amino carboxylic acid NH2-Z-CO2H, together with at least one compatible diluent, carrier, surface active agent or other adjuvant.

A particular sub-group of derivatives of the acids of formula (I) is constituted by the amides of formula (111) RX (CHY) CONHR' (111), where R, X, n and Y have the above-stated meanings and R'is selected from and the residue Z-CO2H of an a-aminocarboxylic acid NH2-Z-CO2H.

The term"corresponding lactones"in the present specification and claims means the lactones of the acids of formula (1), where X = CHOH ; by way of example, when n=2, the lactones would have the formula (IV) In another aspect, the invention provides a method for combatting plant fungi, which comprises applying to the locus thereof at least one compound selected from carboxylic acids of the formula (I) as defined above, including the corresponding lactones and functional derivatives of the carboxylic acid group.

In a further aspect, the invention provides a compound selected from carboxylic acids of formulae : RX (CHY) n-CO2H (la) and RX (CHY) mCONH-Z-CO2H (II) the corresponding lactones and functional derivatives of the carboxylic acid group, and amides of formula : RX (CHY) n CONHR' (Illa), where R is an unsubstituted or substituted aromatic nucleus, X is CHOH or CO, n'is an integer selected from 3,4 and 5, m is 1 or 2, each Y is independently H, C14 alkyl, C, 4 alkoxy, OH, NH2, halogen, substituted OH or substituted NH2, Z is the residue of an a-amino carboxylic acid NH2-Z-CO2H, n"is 2 and R'is selected from and the residue Z-C02H of an a-aminocarboxylic acid NH2-Z-CO2H.

DETAILED DESCRIPTION OF THE INVENTION The compounds useful in the present invention may be prepared by processes known per se. By way of exemple : (a) the compounds where X is CHOH, or the corresponding lactones thereof, may be prepared by reducing the CO to a CHOH group in a the corresponding oxo-analog (b) the compounds where X is CO, may be prepared by acylating a compound RH with a reactive derivative of an acid of formula H02C (CHY) nCO2H ; and in either case (a) or (b), if desired hydrolyzing an ester group to the corresponding acid, or esterifying a free acid group to a corresponding ester, or converting an acid or ester to a corresponding amide.

The functional derivatives referred to above are preferably selected from among salts, esters and amides of the carboxylic acids. Particularly preferred salts are those of the alkali and alkaline earth metals (e. g. Na, K or Ca) or ammonium salts, including salts with primary, secondary or tertiary amines, and quaternary ammonium salts. Presently preferred esters are those with monohydric C, 4 alcohols, such as methanol, ethanol, propanol, isopropanol and the butanols, or with polyhydric alcohols such as ethyleneglycol, 1,3-propyleneglycol, glycerol or polyoxyethyleneglycols.

Presently preferred amides are those derived from the carboxylic acids and ammonia, or primary or secondary amines such as alkylamines or dialkylamines, particularly where"alkyl"is C, 4-alkyi.

As mentioned above, another group of presently preferred functional derivatives of (I) are those of formula RX (CHY) CONHR' (111), where R, X, n and Y have the meanings previously stated, and R'is selected from and the residue Z-C02H of an a-aminocarboxylic acid NH2-Z-CO2H.

In the present specification and claims, the a-aminocarboxylic acid NH2-Z-CO2H means any of the following: alanine, arginine, asparagine, aspartic acid, ß-carboxyaspartic acid, y-carboxyglutamic acid, cysteine, cystine, glutamine, glutamic acid, glycine, histidine, homoserine, hydroxylysine, hydroxyproline, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine and the acid of formula The compatible diluent, carrier, surface active agent or other adjuvant used in the compositions of the invention are those known to the practitioner of agricultural pest control and in particular plant fungus control. Similarly, the inventivity of the method of the invention for combatting fungi resides in use of the plant fungus inhibiting compounds according to the invention, but otherwise the methods known to the practitioner in the art are generally applicable.

As regards the process for preparing the carboxylic acids of or useful in the invention including the corresponding lactones and functional derivatives (e. g. esters or amides) of the carboxylic acid group, where X is CHOH, this comprises reducing the CO to a CHOH group in the analogous compound in which X is CO. The reagents for effecting this reduction, selectively if necessary, are well-known in the art. As is also generally known, there exists an equilibrium between the hydroxy acids and the corresponding lactones which is frequently weighted in favor of the lactones as the more thermodynamically stable entity.

As regards the process for preparing the carboxylic acids including the functional derivatives (e. g. esters or amides) of the carboxylic acid group, where X is CO, this comprises acylating a compound RH with a reactive derivative of an acid of formula H02C (CHY) CO2H, e. g. in a Friedel-Crafts reaction, using for example (where n-2) an anhydride of formula and analogous cyclic anhydrides when n is 3-5. It will be evident that by applying known conversion steps, in the product of reduction or acylation, an ester group may be hydrolyzed to the corresponding acid, or a free acid group may be esterified to give a corresponding ester, or a corresponding amide may be obtained from an acid or ester.

Particular embodiments of the compounds of the invention are the uridine derivatives of the following formulae in which R, n and Y have in general the meanings defined above, while specific examples thereof are appended to the formulae. GC-113 (R = p-methoxyphenyl; n=2, each Y =H) GC-112 (R = p-hydroxyphenyl; n=2, each Y =H) GC-111 (R = p-methoxyphenyl; n=2, each Y =H) GC-110 (R = p-hydroxyphenyl ; n=2, each Y =H) Further particular embodiments of compounds of the invention are constituted by the lactones of formulae (V) and (VI), where Ar is e. g. p-methoxyphenyl or p-hydroxyphenyl: In the present plant fungus inhibiting compounds (I), (II) and (III), R is an unsubstituted or substituted aromatic nucleus, preferably a benzene ring, but it may also be e. g., another carbocyclic aromatic ring such as naphthyl, or a heterocyclic aromatic ring such as furan, thiophene, pyrrole, pyridine, benzopyran or benzothiophene. When R is substituted, the substituent may be, e. g., one or more of hydroxy, C1 4-alkoxy, halogen, cyano, nitro, carboxylic acid, ester or amide, sulfonic acid, ester or amide, sulfone, sulfoxide or halogenated C, 4-alkyl such as chloro-or dichloro-methyl or CF3, amino, mono (Cl 4-alkyl) amino, di (C1 4-alkyl) amino, or Ci. 4-alkyi. In (I), (II) and (III) also, it is presently contemplated that each Y is independently H, C14 alkyl, C, _4 alkoxy) OH, NH2, halogen, substituted OH or substituted NHz. The possible selection of C14 alkyl, C14 alkoxy, OH, NH2, halogen, substituted OH or substituted NH2, in place of Y=H, will of course depend on how these substituents affect the fit of the active fungus-inhibiting species into the relevant enzymatic site. The better Y is fitted into the enzymatic site, the better should be the inhibiting selectivity of a fungicide, and consequently its toxicity would be correspondingly lower. By substituted OH or substituted NHz, in the present context, there are intended the corresponding groups in which H has been replaced by a substituent group (other than C14 alkyl in the case of OH, since this has been mentioned specifically), and in particular acyl inclusive (in the case of NHz), of peptide-forming groups, and sugar and nucleoside residues, and mimetics of peptides and nucleosides, respectively.

A person of the art will appreciate that the compounds useful in the composition and method of the invention can alternatively be defined by the general formula RX (CHY) p (CONH-Z-) qCO2H (Vil) including the corresponding lactones and functional derivatives of the carboxylic acid group, where q is 0 or 1; when q is 0, p is an integer selected from 2,3,4 and 5, and when q is 1, p is 1 or 2; the other symbols in this formula having the previously noted meanings.

Similarly, the compounds of the invention which are believed to be novel and inventive per se can be defined by the above formula (VII) where all symbols have the stated meanings, but with the added proviso that when p is 2, then said compounds are restricted to the amides of the depicted acids with the amine R'NH2, R'having the previously stated meaning.

The present invention moreover provides a composition for combatting plant fungi, which comprises at least one compound having plant fungus inhibiting activity, selected from carboxylic acids of the formulae : RX (CHY) C02H (vil) the corresponding lactones and functional derivatives (such as salts, esters or amides) of the carboxylic acid group, where R is an unsubstituted or substituted aromatic nucleus, X is CHOH or CO, and Y is independently H, C14 alkyl, C14 alkoxy, OH, NHz, halogen, substituted OH or substituted NH2, together with at least one compatible diluent, carrier, surface active agent or other adjuvant. Functional derivatives may correspond with the formula : RX (CHY) CONHR' (IX), where R, X and Y have the meanings set forth above, and R'is selected from and the residue Z-C02H of an a-aminocarboxylic acid NH2-Z-CO2H. Also provided by the invention is a method for combatting plant fungi, which comprises applying to the locus thereof at least one compound selected from compounds of formula (Vlil) and their functional derivatives and lactones, as defined above, preferably in the form of the just-described composition.

Within the definition of formula (VIIl) it is believed that, for example, 2-methyl-3- (p-methoxyphenyl)-3-hydroxypropionic acid and the p- ! actone thereof, are novel compounds.

The invention will be illustrated by the following Examples.

Example I. y-lactone of 4- (p-methoxvphenvl)-4-hydroxybutyric acid (IV : R = p-methoxyphenyl; n = 2, each Y = H."GC-119") 1.4-(p-methoxyphenvl)-4-oxobutyric acid Anisole (10.80g ; 0.1 M) was dissolved in of anhydrous dichloromethane (130 ml). Succinic anhydride (10.00 g ; 0.1 M) was added to the solution, stirred by a magnetic stirrer, and after dissolution of anhydride, anhydrous AIC13 (33.34 g ; 0.25 M) was added to the solution. The reaction proceeded vigorously at room temperature, and hydrogen chloride evolution continued for three hours. The reaction mixture was left overnight. The next day, the reaction mixture was hydrolyzed with ice-water and diluted hydrochloric acid (1 : 4), and dichloromethane was removed on Buchi Rotovapor, the solid was filtered off and dried in vacuo. The residue was 4- (p-methoxyphenvl)-4-oxobutyric acid (18.0 g ; 86.5%), m. p. 145°C. It was crystallized from a mixture of acetone/n-hexane (1 : 1), m. p 146°C (uncorrected).

2.4- (p-methoxvphenyl-y-butyrolactone The 4- (p-methoxyphenvl)-4-oxobutyric acid 0.00192 M) was dissolved in ethyl acetate (10 ml). Acetic acid (0.5 ml) and palladium on activated carbon (0.032 g ; 10% Pd) were added to the solution. The reaction mixture was hydrogenated at 50-53°C over 24 hours, filtered, and ethyl acetate and acetic acid were removed from the filtrate in vacuo. The residue (0.386 g) was dissolved in dichloromethane (10 ml), washed with 5% aqueous NaHC03 and dried with anhydrous MgS04. Dichloromethane was removed in vacuo. The residue constituted 0.304 g (82.3%) of white crystals, m. p. 53-54°C. The lactone was soluble in acetone, dichloromethane and ether, and had low solubility in n-hexane.

Example la. y-lactone of 4- (p-methoxvphenvl)-4-hydroxv-3-methylbutyric acid (IV : R = p-methoxyphenyl; COCHYCHY = COCH2CHCH3."GC-140").

This compound was prepared analogously to Example 1.

Example 2. Y-lactone of 4-(p-hvdroxvphenvl)-4-hvdroxybutvric acid (IV : R = p-hydroxyphenyl; n = 2, each Y = H."GC-118") 1.4-(p-hvdroxvphenvl)-4-oxobutyric acid Water (1 ml) was added to 4- (p-methoxyphenyl)-4-oxo-butyric acid (0.500 g ; 0.0024 M) dissolved in 4 mi of 33% solution of hydrogen bromide in acetic acid. The reaction mixture was refluxed for 6 hours. The solvent was removed in vacuo, the dark residue was dissolved in acetone (5 ml). Carbon tetrachloride (10 ml) and activated carbon (Norit SA3 ; 0.1 g) were added to the solution. The mixture was filtered off, the solvents were removed in vacuo and the residue was crystallized from a mixture of n-hexane/acetone (2: 1).

The crystailization product constituted 0.368 g (78.9%) of slightly yellow crystals, m. p. 154-155°C. The product was homogeneous on silica gel thin layers with n-hexane/acetone (5 : 4) as eluent (Rf = 0.12).

2.4- (p-hydroxvphenyl)-v-butyrolactone The 4- (p-hydroxyphenvl)-4-oxobutyric acid (0.202g; 0.00104 M) was dissolved in ethyl acetate (3 ml). Acetic acid (0.5 ml) and palladium on activated carbon (17.8 mg; 10% Pd) were added to the solution. The reaction mixture was hydrogenated at 52°C over 18 hours, filtered, and the solvent was removed from the filtrate in vacuo. The white crystalline residue (0.184 g; 99.5%) had m. p. 102-3°C. It was homogeneous on silica gel thin layers, with 1: 1 n-hexane/acetone as eluent (Rf = 0.39).

Example 3. N-F4-(p-methoxyphenvl)-4-hvdroxvbutvrvllqlvcine ethvl ester.

(III : (R = p-methoxyphenyl; n = 2, Y = H; R'= CH2CO2Et"GC-127") 4- (p-methoxyphenyl)-4-oxobutyric acid (0.208 g ; 0. 001 M) was dissolved in pyridine (3 ml) ; to this solution there were added glycine ethyl ester hydrochloride (0.139 g; 0.001 M) and water (3 ml). The mixture was stirred until glycine ethyl ester hydrochloride was dissolved.

Dicyclohexylcarbodiimide (0.258 g ; 0.00125 M) was added to the solution, and the reaction mixture was stirred for 24 hours at room temperature. The precipitated dicyclohexylurea was filtered off and the pyridine and water were removed in vacuo. The residue (0.315 g) was crystallized from chloroform-hexane mixture, to give N- 4- (p-methoxyphenyl)-4-oxobutyryllglycine ethyl ester (0.26 g; 88.7%), m. p.

85°C.

The thus-obtained product (0.073 g ; 0.00025 M) was dissolved in methanol (5 mi) ; acetic acid (0.5 ml) and palladium on activated carbon (16 mg; 10% Pd) were added to the solution. The mixture was hydrogenated at room temperature over 24 hours. The catalyst was removed by filtration, and the solvent was evaporated in vacuo. The white crystalline residue was N- 4- (p-methoxyphenyl)-4-hydroxybutyryl glycine ethyl ester (0.068 g ; 92%).

The structure of the product was confirmed by'H-NMR spectroscopy. The potassium salt of N- 4- (p-methoxyphenyl)-4-hydroxybutyryl glycine was prepared by hydrolysis of the ethyl ester with an equimolar quantity of potassium hydroxide in methanol.

Example 4.

5'r4-(p-methoxyphenvl)-4-oxobutvrylamidol-5'-deOxyuridine (GC-111) (III: R = p-methoxyphenyt; X = CO ; n = 2, each Y = H; R'= 5'-deoxyuridin-5'-yl) and 5' 4- (p-methoxyphenvi)-4-hydroxvbutyrylamidol-5'-deoxyuridine (GC-113) (III: R = p-methoxyphenyl; X = CHOH; n = 2, each Y = H; R'= 5'-deoxyuridin-5'-yl) 4- (p-methoxyphenyl)-4-oxobutyric acid (0.104 g ; 0.0005 M) was dissolved in pyridine (3.5 ml); to this solution there were added 5'-amino-5'-deoxyuridine (0.122 g ; 0.0005 M) and water (3,5 ml).

Dicyclohexylcarbodiimide (0.155 g ; 0.00075 M) was added to the solution, and the reaction mixture was stirred for 24 hours at room temperature. The precipitated dicyclohexylurea 95%) was filtered off and the pyridine and water were removed in vacuo. The residue (0.289 g) was purified by column chromatography on silica gel, using 4 : 1 ethyl acetatelmethanol as eluent, to give GC-111 (0.206 g ; 95%).

The thus-obtained GC-111 (0.038 g ; 0.000877 M) was dissolved in methanol (4 ml) ; acetic acid (0.2 ml) and palladium on activated carbon (11 mg; 10% Pd) were added to the solution. The mixture was hydrogenated at 50-53° and atmospheric pressure over 24 hours. The catalyst was removed by filtration, and the solvent was evaporated in vacuo. The residue was GC-113 (0.038 g ; 100%). The structure of the product was confirmed by 'H-NMR spectroscopy.

Example 5.

5'f4- (p-hydroxvphenyl)-4-oxobutvrvlamido-5'-deoxyuridine (GC-110) R = p-hydroxyphenyl ; X = CO ; n = 2, each Y = H; R'= 5'-deoxyuridin-5'-yl) and 5r4-(p-hydroxyphenvl)-4-hydroxybutyrylamidol-5-deOxyuridine (GC-112).

(III: R = p-hydroxyphenyl; X = CHOH; n = 2, each Y = H; R'= 5-deoxyuridin-5-yl) 4- (p-hydroxyphenyl)-4-oxobutyric acid (0.097 g ; 0.0005 M) and 5'-amino-5'-deoxyuridine (0.122 g ; 0.0005 M) were dissolved in pyridine (3 ml); to this solution there was added water (4 ml). Dicyclohexylcarbodiimide (0.155 g ; 0.00075 M) was added to the solution, and the reaction mixture was stirred for 24 hours at room temperature. The precipitated dicyclohexylurea was filtered off and the pyridine and water were removed in vacuo. The residue (0.262 g) was purified by column chromatography on silica gel, using 4 : 1 : 0.1 ethyl acetate/methanol/acetic acid as eluent, to give GC-110 (0.070 g ; 33%), Rf = 0.40 in 4: 1 : ethyl acetate/methanol, m. p. 155-160°C. The structure of the product was confirmed by'H-NMR spectroscopy.

The thus-obtained GC-110 (0.068 g ; 0.00162 M) was dissolved in methanol (4 ml) ; acetic acid (0.2 ml) and palladium on activated carbon (20 mg ; 10% Pd) were added to the solution. The mixture was hydrogenated at 50-53° and atmospheric pressure over 24 hours. The catalyst was removed by filtration, and the solvent was evaporated in vacuo. The residue was practically pure GC-112 (0.063 g ; 92.6%). The structure of the product was confirmed by'H-NMR spectroscopy.

Example 6.7-(p-methoxyphenvl)-7-hydroxyheptanoic acid (I : R =-methoxyphenyl; X = CHOH; n = 5, each Y = H) and its lactone (V : Ar = p-methoxyphenyi) 1. p-methoxvphenvl)-7-oxoheptanoic acid Using known methods, pimelic acid monoethyl ester was reacted with oxalyl chloride to give s-ethoxycarbonylhexanoyl chloride, which was in turn reacted with anisole (AIC13) giving (V)-ethyl ester, this being hydrolyzed with methanolic KOH followed by acidification (10% HCI) to give the oxo-acid.

2.7-(p-methoxvPhenvl)-7-hvdroxyheptanoic acid The 7- (p-methoxyphenyl)-7-oxoheptanoic acid M) was dissolved in methanol (5 ml). Acetic acid (0.2 ml) and palladium on activated carbon (21 mg ; 10% Pd) were added to the solution. The reaction mixture was hydrogenated at room temperature and atmospheric pressure over 24 hours, filtered, and methanol and acetic acid were removed from the filtrate in vacuo. The residue (0.115 g) constituted the hydroxy-acid. The structure of the product was confirmed by'H-NMR spectroscopy.

3.7-p-methoxvphenvl)-7-hvdroxyheptanoic acid lactone The hydroxy acid (0.063g; 0.00025 M) was dissolved in pyridine (5 ml). and p-toluenesulfonyl chloride 0.00027 M) was added to the solution with stirring, which was continued for 24 hours at room temperature. The pyridine was removed in vacuo and the residue was extracted with ethyl acetate. The extract was washed with water, dried with anhydrous MgS04, filtered and ethyl acetate was removed in vacuo. The residue constituted 0.045 g of the desired lactone. The structure of the product was confirmed by 'H-NMR spectroscopy.

Example 7. N-f4- (-methoxvphenvl)-4-hydroxv-3-methylbuytryll-aminoacetic acid (II : R = p-methoxyphenyl; X = CHOH; (CHY) m= CH (CH3) CH2 ; Z = CHz) and its lactone (Vl : Ar = p-methoxyphenyl) 1. N- 4- (p-methoxvphenyl)-4-oxo-3-methvlbuytryll-aminoacetic acid Using known methods, a-bromo-p-methoxypropiophenone was reacted with diethyl malonate (NaOMe), followed by hydrolysis and simultaneous decarboxylation to give 3-p-methoxybenzoylbutyric acid. The latter was then reacted with glycine ethyl ester (DCC) to give (Vl)-ethyl ester, this being hydrolyzed with methanolic KOH followed by acidification (10% HCI) to give the oxo-acid.

2. N-f4- (p-methoxvphenvl)-4-hydroxy-3-methylbuytryil-aminoacetic acid The N- 4- (p-methoxyphenyl)-4-oxo-3-methylbuytryl-aminoacetic acid (0.140g ; 0.0005 M) was dissolved in methanol (5 ml). Acetic acid (0.2 ml) and palladium on activated carbon (25 mg; 10% Pd) were added to the solution.

The reaction mixture was hydrogenated at 50-53°C and atmospheric pressure over 24 hours, filtered, and methanol and acetic acid were removed from the filtrate in vacuo. The residue (0.130 g) constituted the hydroxy-acid. The structure of the product was confirmed by'H-NMR spectroscopy.

3. N- 4- (p-methoxyphenvl)-4-hydroxy-3-methylbuytryll-aminoacetic acid lactone The hydroxy acid (0.070g; 0.00025 M) was dissolved in pyridine (10 ml) and p-toluenesulfonyl chloride 0.00027 M) was added to the solution with stirring, which was continued for 18 hours at room temperature.

The pyridine was removed in vacuo and the residue was extracted with ethyl acetate. The extract was washed with water, dried with anhydrous MgS04, filtered and ethyl acetate was removed in vacuo. The residue constituted 0.050 g of the desired lactone. The structure of the product was confirmed by 'H-NMR spectroscopy.

Example 8: 2-methvl-3- (p-methoxyphenyl)-3-hydroxypropionic acid and its -lactone (VIII : R = p-methoxyphenoxy, Y = methyl; and ß-lactone).

1. Propionyl chloride was prepared by mixing potassium propionate (32.42 g; 0.289 M) with benzoyl chloride (89.38 g; 0.636 M), when a highly exothermic reaction ensued, which necessitated water cooling of the reaction flask. The desired product (21.66 g ; 81 %) distilled at 74°C.

2. S- (propionyl) thiophenol.

Propionyl chloride (9.25 g ; 0.1 M) was added dropwise to a mixture of thiphenol (10.3 ml ; 0.1 M) and pyridine (8.1 mi in methylene chloride (100 ml) under argon, in an ice-cooled 250 ml flask. The mixture was stirred for 5 minutes in the ice-bath and then for 30 minutes at room temperature. Water (100 ml) was added, the organic layer was separated, the aqueous layer was washed with methylene chloride (25 ml), and the combined organic layer and washings was dried with MgS04, followed by distillation, to give the desired product (15.51 g; 94%), R, = 0.53 (1: 0.2 hexane/ethyl acetate), Rf 0.82 (1 : 1 hexane/ethyl acetate).

3. {3-lactone of 2-methyl-3- (p-methoxyphenyl)-3-hydroxvpropionic acid To a solution (10 ml of 2N in heptane/THF/ethylbenzene) of lithium diisopropylamine, LiN (i-Pr) 2, in THF 100 ml, cooled to-78°C, S- (propionyl) thiophenol (3.32 g) was added via syringe, the mixture was stirred for 35 minutes, then allowed to reach room temperature, after which it was again cooled to-78°C, anisaldehyde (2.72 g ; 0.02 M) was added via a TeflonTM pipe, the mixture was stirred for 30 minutes, brought to room temperature over 1.5 hours and 100 ml aqueous (17%) NH4CI was added.

The organic layer was separated, TGF distille, the residue diluted with diethyl ether, treated with NaHC03 with liberation of C02, the ether layer was separated, dried (MgS04) and the ether rotor-evaporated to give a residue (5.112 g) which was subjected for 30 minutes to oil-pump vacuum, giving the crude product (4.97 g). A chromatogram (1 : 0.2 hexane/ethyl acetate) gave five spots :. Rf = 0.00 (average intensity, UV); 0.24 (intensive); 0.36 (intensive) ; 0.54 (weak intensity); 0.67 (weak intensity). Subjecting the product to prolonged vacuum gave 3.759 g residue. (Note : in the same system, Rf for acetol (trans) = 0. 64 ; S-(propionyl) thiophenol = 0. 55 ; anisaldehyde = thiophenol = 0.68.

Extraction of the aqueous phase with ether (50 mi), drying the ethereal phase (MgSO4) and distillation gave a colorless liquid residue (0.167 g). A chromatogram (1 : 0.2 hexane/ethyl acetate) gave three spots: Rf = 0.00 (initially the most intensive); 0.26; and 0.71. The spot at Rf = 0.36 was shown to be lactone on developing with phosphoric-molybdic acid; a similar reaction of the spot at Rf 0.00 suggests that this may be 2-methyl-3-(p-methoxyphenyl)-3-hydroxypropionic(p-methoxyphe nyl)-3-hydroxypropionic acid. Development of the spot Rf = 0.24 using 2 : 4-DNPH suggests that thi is anisaldehyde. The lactone was further purified by extraction with hexane and chromatographing on silica gel with 5 : 1 hexane/ethyl acetate; the pure product in this solvent had Rf = 0.45. It was stored in the refrigerator and was used for biological testing.

PLANT FUNGUS INHIBITING ACTIVITY Methods and materials The compounds tested were dissolved in aqueous ethanol, if necessary with the aid of dimethylformamide or dimethylsulfoxide. The nutrient medium was potato agar containing chloramphenicol as antimicrobial agent ; it was brought to 40°C before adding the solutions under test.

Procedure The nutrient medium was brought to 40°C before adding the solutions under test. These were introduced to the nutrient medium in a quantity calculated according to the initial and final concentrations required. Test plates of 45 mm and 90 mm diameter were filled in succession with nutrient medium/test solution mixture. In control experiments, the nutrient medium was mixed only with an identical quantity of solvent, as used in the solutions being tested.

An agar disc with 5 mm diameter of the original edges of growing fungus was dispersed in the center of a plate containing either medium/test solution mixture, or a control. The fungi listed in the Table (below) were used.

The growth area of fungus in each experiment was determined by measuring the diameters of the growing fungi once in 1-2 days, according to their growth rate in the controls. The LD50 values could thus be calculated. Results are shown in the following Table Compound Fungus Inhibitory tested Concentration (tg/ml) GC-110 Sclerotinia sclerotiorum 1 5 GC-113 Colletotrichum acutatum 1 1 Pythium aphanidermatum 1 5 GC-118 Pythium aphanidermatum 1 1 Fusarium oxysporum f. sp. lycopersici 1 10 GC-119 Trichodermaharzianum T39 1 Pythium aphanidermatum 1 0.1 Colletotrichum acutatum 1 10 Botrytis cinerea B16 10 Fusarium oxysporum f. sp. lycopersici 1 5 GC-140 Trichodermaharzianum T39 10 Colletotrichum acutatum 1 0.5 Rhizoctonia solani 1 Botrytis cinerea B16 3 Sclerotinia sclerotiorum 1 5 Fusarium oxysporum f. sp. lycopersici 1 0.5 Pythium aphanidermatum 1 1 GC-165 Trichodermaharzianum T39 10 Colletotrichum acutatum 1 10 Rhizoctonia solani 0.1 Botrytis cinerea B16 0.05 Sclerotinia sclerotiorum 1 5 Fusarium oxysporum f. sp. lycopersici 1 5 Pythium aphanidermatum 1 3 Conclusions The compounds having plant fungus inhibiting activity according to the invention demonstrated good inhibition of the various plant fungi on which they were tested.

While particular embodiments of the invention have been particularly described hereinabove, it will be appreciated that the present invention is not limited thereto, since as will be readily apparent to skilled persons, many modifications or variations can be made. Such modifications or variations which have not been detailed herein are deemed to be obvious equivalents of the present invention.