AN ENANTIOSPECIFIC PROCESS FOR THE PREPARATION OF (R) AND (S) ENANTIOMERS OF SEX PHEROMONOES OF THE LONG TAILED MEALY BUG

Abstract

The present invention relates to an enantiospecific process for the preparation of (R) and (S) enantiomers of sex pheromones of the long-tailed mealybug with high enantiopurity.

##STR00001##

Claims

1. An enantiospecific process for preparation of (R) and (S) enantiomers of sex pheromones of the long tailed mealybug comprising the steps of: a) oxidizing (+) oxobornylacetate(+)-(2) or ()-(2) using suitable oxidizing agent in presence of sulfuric acid (H.sub.2SO.sub.4) followed by acetate hydrolysis using suitable base to obtain compound (+)-3 or ()-3 respectively; ##STR00018## b) oxidizing alcohol (+)-3 or ()-3 of step (a) using Cornforth reagent to obtain lactone (+)-4 or ()-4 respectively; ##STR00019## c) hydrolyzing lactone(+)-4 or ()-4 of step (b) with suitable hydrolyzing agent in methanol to give ,-unsaturated cyclopentenone(+)-5 or ()-5 respectively; ##STR00020## d) subjecting the cyclopentenone(+)-5 or ()-5 of step (c) To luche reduction to afford allylic alcohol 6 or 6; e) subjecting the allylic alcohol 6 or 6 of step (d) to deoxygenation using dehydroxylation agent in tetrahydrofuran (THF) followed by reduction to afford 7b and (+)-7a or 7b and ()-7a respectively; ##STR00021## f) subjecting alcohol (+)-7a or ()7a of step (e) to acylation to afford compound (+)- or ()-pheromone respectively. ##STR00022##

2. The process as claimed in claim 1, wherein said suitable oxidizing agent in step (a) is hydrogen peroxide in acetic acid.

3. The process as claimed in claim 1, wherein said suitable base in step (a) is an inorganic base; said base is selected from sodium carbonate, sodium bicarbonate and calcium carbonate; said base is potassium carbonate.

4. The process as claimed in claim 1, wherein said cornforth reagent of step (b) is Pyridiniumdichromate (PDC).

5. The process as claimed in claim 1, wherein said suitable hydrolyzing agent of step (c) is p-Toluenesulfonic acid.

6. The process as claimed in claim 1, wherein said luche reduction in step (d) is carried out in presence of cerium (III) chloride heptahydrate and sodium borohydride.

7. The process as claimed in claim 1, wherein said deoxygenation agent of step (e) is sodium cyanoborohydride and boron trifluoride-etherate.

8. The process as claimed in claim 1, wherein said acylation reaction in step (f) is carried out using acylating agent, base and catalyst; wherein said acylating agent is selected from acetic anhydride, acetyl chloride; wherein said acylating agent is acetic anhydride, wherein said base in step f is selected from the group consisting of dimethylamine, diethylamine, trimethylamine, triethylamine, tributylamine, dimethylaniline, pyridine or mixtures thereof, said base is selected from triethylamine in presence of acylation catalyst such as 4-dimethylaminopyridine.

9. The process as claimed in claim 1, wherein said process for preparation of (R)-()-pheromone comprising the steps of: a) adding acetic acid, hydrogen peroxide and H.sub.2SO.sub.4 to ()5-oxobornylacetate and stirred for the time ranging from 24 to 26 h at the temperature ranging from 25 to 30 C. followed by work up, concentration and addition of potassium carbonate and further stirring for the time period ranging from 3 to 4 h to obtain (3aS,5S,6aR)-5-hydroxy-3a,4,4-trimethylhexahydro-2H-cyclopenta[b]furan-2-one (()-3); b) adding pyridinium dichromate to a solution of compound of step (a) followed by stirring for the time period ranging from 8 to 10 h at the temperature ranging from 25 to 30 C. to obtain 3aS,6aR)-3a,4,4-trimethyltetrahydro-2H-cyclopenta[b]furan-2,5(3H)-dione (()-4); c) refluxing, the reaction mixture of P-Toluene sulphonic acid and a solution of compound of step (b) in methanol for the time period ranging from 24 to 26 h at the temperature ranging from 65 C. to 70 C. to obtain methyl (R)-2-(1,5,5-trimethyl-4-oxocyclopent-2-en-1-yl)acetate (()-5); d) adding cerium(III) chloride heptahydrate and sodium borohydride to a cooled solution of compound of step (c) in methanol followed by stirring the reaction mixture for the time period ranging from 1 to 2 h at the temperature ranging from 25 C. to 30 C. to obtain methyl 2-((1R)-4-hydroxy-1,5,5-trimethylcyclopent-2-en-1-yl)acetate (6); e) adding boron trifluoride diethyl etherate and sodiumcyanoborohydride to a cooled solution of compound of step (d) in tetrahydrofuran followed by refluxing the reaction mixture for the time period ranging from 8 to 10 h at the temperature ranging from 66 C. to 70 C. to obtain methyl (R)-2-(1,5,5-trimethylcyclopent-2-en-1-yl)acetate followed by adding lithium aluminium hydride (LAH) to a cold solution of compound of step (e) in tetrahydrofuran followed by stirring the reaction mixture for the time period ranging from 2 to 3 h at the temperature ranging from 25 C. to 30 C. to obtain (R)-2-(1,5,5-trimethylcyclopent-2-en-1-yl)ethan-1-ol (()-(7a); f) stirring the reaction mixture of compound of step (f) in dichloromethane, triethylamine, acetic anhydride and 4-dimethylaminopyridine for the time period ranging from 3 to 4 h at the temperature ranging from 25 C. to 30 C. to obtain (R)-2-(1,5,5-trimethylcyclopent-2-en-1-yl)ethyl acetate.

10. The process as claimed in claim 1, wherein said process for preparation of (S)-(+)-pheromone comprising the steps of: a) adding acetic acid, hydrogen peroxide and H.sub.2SO.sub.4 to (+)-5-oxobornylacetate and stirred for the time period ranging from 24 to 26 h at the temperature ranging from 25 C. to 30 C. followed by work up, removal of solvent and addition of potassium carbonate and further stirring for the time period ranging from 3 to 4 h to obtain (3aS,5S,6aR)-5-hydroxy-3a,4,4-trimethylhexahydro-2H-cyclopenta[b]furan-2-one ((+)-3); b) adding pyridinium dichromate to a solution of compound of step (a) followed by stirring for the time period ranging from 8 to 10 h at the temperature ranging from 25 C. to 30 C. to obtain (3aS,6aR)-3a,4,4-trimethyltetrahydro-2H-cyclopenta[b]furan-2,5(3H)-dione ((+)-4); c) refluxing the reaction mixture of p-toluene sulphonic acid and a solution of compound of step (b) in methanol for the time period ranging from 24 to 26 h at the temperature ranging from 65 C. to 70 C. to obtain methyl (S)-2-(1,5,5-trimethyl-4-oxocyclopent-2-en-1-yl)acetate ((+)-5); d) adding Cerium(III) chloride heptahydrate and sodium borohydride to a cold solution of compound of step (c) in methanol followed by stirring the reaction mixture for the time period ranging from 1 to 2 h at the temperature ranging from 25 C. to 30 C. to obtain methyl 2-((1S)-4-hydroxy-1,5,5-trimethylcyclopent-2-en-1-yl)acetate (6); e) adding boron trifluoride, diethyl etherate and sodiumcyanoborohydride to a cold solution of compound of step (d) in tetrahydrofuran followed by refluxing the reaction mixture for 8 to 10 hours at the temperature ranging from 66 C. to 70 C. to obtain methyl (S)-2-(1,5,5-trimethylcyclopent-2-en-1-yl)acetate followed by adding lithiumaluminiumhydride (LAH) to a cold solution of compound of step (e) in tetrahydrofuran followed by stirring the reaction mixture for the time period ranging from 2 to 3 h at the temperature ranging from 25 C. to 30 C. to obtain (S)-2-(1,5,5-trimethylcyclopent-2-en-1-yl)ethan-1-ol ((+)-(7a); f) stirring the reaction mixture of compound of step (f) in dichloromethane, triethylamine, acetic anhydride and 4-Dimethylaminopyridine for the time period ranging from 3 to 4 h at the temperature ranging from 25 C. to 30 C. to obtain (S)-2-(1,5,5-trimethylcyclopent-2-en-1-yl)ethyl acetate.

11. Novel intermediates of process as claimed in claim 1, wherein intermediates of said process are selected from (3aS,5S,6aR)-5-hydroxy-3a,4,4-trimethylhexahydro-2H-cyclopenta[b]furan-2-one, (3aS,6aR)-3a,4,4-trimethyltetrahydro-2H-cyclopenta[b]furan-2,5(3H)-dione, methyl-2-(1,5,5-trimethyl-4-oxocyclopent-2-en-1-yl)acetate, methyl 2-((1R)-4-hydroxy-1,5,5-trimethylcyclopent-2-en-1-yl)acetate.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0022] The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.

[0023] The expression ()-1 or (R)-1 or () pheromone or (R)-enantiomer or (R)-pheromone or () 2-(1,5,5-trimethylcyclopent-2-en-1-yl)ethyl acetate or 2-[(1R)-1,5,5-trimethylcyclopent-2-en-1-yl]ethyl acetate are used interchangeably throughout the specification.

[0024] Similarly, the expression (+)-1 or (S)-1 or (+) pheromone or (S)-enantiomer or (S)-pheromone or (+) 2-(1,5,5-trimethylcyclopent-2-en-1-yl)ethyl acetate or 2-[(1S)-1,5,5-trimethylcyclopent-2-en-1-yl]ethyl acetate are used interchangeably throughout the specification and the same may be appreciated as such by the person skilled in the art.

[0025] The present invention provides a novel synthetic route for the preparation of enantiomers (represented by (+) 1 and () 1 of sex pheromones of the long-tailed mealybug with high enantiopurity having significant biological activity.

##STR00007##

[0026] In an embodiment, the present invention provides an enantiospecific process for preparation of (R) and (S) enantiomers of sex pheromones of the long-tailed mealybug comprising the steps of: [0027] a) oxidizing (+)bornylacetate(+)-(2) using suitable oxidizing agent in presence of sulfuric acid (H.sub.2SO.sub.4) followed by acetate hydrolysis using suitable base to obtain compound (+)-3; [0028] b) oxidizing alcohol (+)-3 of step (a) using Cornforth reagent to obtain lactone (+)-4; [0029] c) hydrolyzing lactone(+)-4 of step (b) with suitable hydrolyzing agent in methanol to give --unsaturated cyclopentenone(+)-5; [0030] d) subjecting the cyclopentenone(+)-5 of step (c) to luche reduction to afford allylic alcohol 6; [0031] e) subjecting the allylic alcohol 6 of step (d) to deoxygenation using dehydroxylation agent in tetrahydrofuran (THF) followed by reduction to afford 7b and (+)-7a; [0032] f) subjecting alcohol (+)-7a of step (e) to acylation to afford compound (+)-pheromone. [0033] Using similar procedure, ()-pheromone can be synthesized starting from ()bornylacetate ()-(2) through the intermediacy of ()-3, ()-4, ()-5, 6 and ()7a.

[0034] In preferred embodiment, said suitable oxidizing agent in step (a) is selected from hydrogen peroxide, preferably the oxidizing agent is hydrogen peroxide in acetic acid.

[0035] In another preferred embodiment, said suitable base in step (a) is an inorganic base; said base is selected from sodium carbonate, sodium bicarbonate and calcium carbonate, preferably said base is potassium carbonate.

[0036] The Cornforth reagent of step (b) is Pyridiniumdichromate (PDC).

[0037] In still another preferred embodiment, said suitable hydrolyzing agent of step (c) is p-Toluenesulfonic acid.

[0038] The luchereduction in step (d) is carried out in presence of cerium (III) chloride heptahydrate and sodium borohydride.

[0039] In yet another preferred embodiment, said deoxygenation agent of step (e) issodium cyanoborohydride and boron trifluoride-etherate.

[0040] The acylation reaction in step (f) is carried out using acylating agent, base and catalyst.

[0041] In still yet another preferred embodiment, said acylating agent of step (f) is selected from acetic anhydride, acetyl chloride, preferably said acylating agent is acetic anhydride.

[0042] In still yet another preferred embodiment, said base is selected from the group consisting of dimethylamine, diethylamine, trimethylamine, triethylamine, tributylamine, dimethylaniline, pyridine or mixtures thereof, preferably triethylamine in presence of suitable acylation catalyst such as 4-dimethylaminopyridine or the like.

[0043] In still yet another preferred embodiment, the present invention provides an enantiospecific process for preparation of (R)-()-pheromone of the long-tailed mealybug with high enantiopurity comprising the steps of: [0044] a) adding acetic acid, hydrogen peroxide and H.sub.2SO.sub.4 to ()5-oxobornylacetate and stirred for the time ranging from 24 to 26 h at the temperature ranging from 25 to 30 C. followed by work up, concentration and addition of potassium carbonate and further stirring for the time period ranging from 3 to 4 h to obtain (3aS,5S,6aR)-5-hydroxy-3a,4,4-trimethylhexahydro-2H-cyclopenta[b]furan-2-one (()-3); [0045] b) adding pyridinium dichromate to a solution of compound of step (a) followed by stirring for the time period ranging from 8 to 10 h at the temperature ranging from 25 to 30 C. to obtain 3aS,6aR)-3a,4,4-trimethyltetrahydro-2H-cyclopenta[b]furan-2,5(3H)-dione (()-4); [0046] c) refluxing, the reaction mixture of P-Toluene sulphonic acid and a solution of compound of step (b) in methanol for the time period ranging from 24 to 26 h at the temperature ranging from 65 C. to 70 C. to obtain methyl (R)-2-(1,5,5-trimethyl-4-oxocyclopent-2-en-1-yl)acetate (()-5); [0047] d) adding cerium(III) chloride heptahydrate and sodium borohydride to a cooled solution of compound of step (c) in methanol followed by stirring the reaction mixture for the time period ranging from 1 to 2 h at the temperature ranging from 25 C. to 30 C. to obtain methyl 2-((1R)-4-hydroxy-1,5,5-trimethylcyclopent-2-en-1-yl)acetate (6); [0048] e) adding boron trifluoride diethyl etherate and sodiumcyanoborohydride to a cooled solution of compound of step (d) in tetrahydrofuran followed by refluxing the reaction mixture for the time period ranging from 8 to 10 h at the temperature ranging from 66 C. to 70 C. to obtain methyl (R)-2-(1,5,5-trimethylcyclopent-2-en-1-yl)acetate; [0049] f) adding lithium aluminium hydride (LAH) to a cold solution of compound of step (e) in tetrahydrofuran followed by stirring the reaction mixture for the time period ranging from 2 to 3 h at the temperature ranging from 25 C. to 30 C. to obtain (R)-2-(1,5,5-trimethylcyclopent-2-en-1-yl)ethan-1-ol (()-(7a); [0050] g) stirring the reaction mixture of compound of step (f) in dichloromethane, triethylamine, acetic anhydride and 4-dimethylaminopyridine for the time period ranging from 3 to 4 h at the temperature ranging from 25 C. to 30 C. to obtain (R)-2-(1,5,5-trimethylcyclopent-2-en-1-yl)ethyl acetate.

[0051] The enantiospecific process for the preparation of (R)-()-pheromone of the long-tailed mealybug is as shown in scheme 3 below:

##STR00008##

[0052] The ketone ()-(2) is subjected to Baeyer-Villiger oxidation using H.sub.2O.sub.2 in acetic acid in presence of H.sub.2SO.sub.4 followed by acetate hydrolysis using K.sub.2CO.sub.3. Under these conditions, we obtained the compound ()-3 which is confirmed by X-ray crystal structure analysis. The alcohol ()-3 is oxidized to ketone ()-4 using Pyridiniumdichromate (PDC). The lactone ()-4 is hydrolysed with p-Toluenesulfonic acid (PTSA) in methanol to give --unsaturated cyclopentenone ()-5. The allylic alcohol 6 obtained by luche reduction of ()-5 is subjected to dehydroxylation using BF.sub.3.etherate and sodiumcyanoborohydride in dry THF to give a mixture of regioisomeric products. The ester is reduced with LAH and the regioisomers7b and ()-7a can be separated at this stage. The alcohol ()-7a is acylated to give the target compound ()-pheromone. The same route is followed for the synthesis of the other antipode (S)-(+)-pheromone. The optical rotations also showed the same magnitude but with an inverse sign.

[0053] The regioisomeric mixture obtained in the step (e) is used to prepare the title compound. The compound is then dissolved in tetrahydrofuran (THF), cooled to 0 C. followed by addition of Lithium aluminium hydride (LAH) and stirred at room temperature for 2 h. The reaction mixture was quenched with saturated Sodium sulfate (Na.sub.2SO.sub.4), ethyl acetate was added and the organic layer was separated, dried and purified by column chromatography. Both the regioisomers are separated by flash column chromatography.

[0054] In still yet another preferred embodiment, the present invention provides an enantioselective process for preparation of (S)-(+)-pheromone of the long-tailed mealybug with high enantiopurity wherein the process comprising the steps of: [0055] a) adding acetic acid, hydrogen peroxide and H.sub.2SO.sub.4 to (+)-5-oxobornylacetate (+)-2 and stirred for the time period ranging from 24 to 26 h at the temperature ranging from 25 C. to 30 C. followed by work up, removal of solvent and addition of potassium carbonate and further stirring for the time period ranging from 3 to 4 h to obtain (3aS,5S,6aR)-5-hydroxy-3a,4,4-trimethylhexahydro-2H-cyclopenta[b]furan-2-one ((+)-3); [0056] b) adding pyridinium dichromate to a solution of compound of step (a) followed by stirring for the time period ranging from 8 to 10 h at the temperature ranging from 25 C. to 30 C. to obtain (3aS,6aR)-3a,4,4-trimethyltetrahydro-2H-cyclopenta[b]furan-2,5(3H)-dione ((+)-4); [0057] c) refluxing the reaction mixture of p-toluene sulphonic acid and a solution of compound of step (b) in methanol for the time period ranging from 24 to 26 h at the temperature ranging from 65 C. to 70 C. to obtain methyl (S)-2-(1,5,5-trimethyl-4-oxocyclopent-2-en-1-yl)acetate ((+)-5); [0058] d) adding Cerium(III) chloride heptahydrate and sodium borohydride to a cold solution of compound of step (c) in methanol followed by stirring the reaction mixture for the time period ranging from 1 to 2 h at the temperature ranging from 25 C. to 30 C. to obtain methyl 2-((1S)-4-hydroxy-1,5,5-trimethylcyclopent-2-en-1-yl)acetate (6); [0059] e) adding boron trifluoride, diethyl etherate and sodiumcyanoborohydride to a cold solution of compound of step (d) in tetrahydrofuran followed by refluxing the reaction mixture for 8 to 10 hours at the temperature ranging from 66 C. to 70 C. to obtain methyl (S)-2-(1,5,5-trimethylcyclopent-2-en-1-yl)acetate; [0060] f) adding lithiumaluminiumhydride (LAH) to a cold solution of compound of step (e) in tetrahydrofuran followed by stirring the reaction mixture for the time period ranging from 2 to 3 h at the temperature ranging from 25 C. to 30 C. to obtain (S)-2-(1,5,5-trimethylcyclopent-2-en-1-yl)ethan-1-ol ((+)-(7a); [0061] g) stirring the reaction mixture of compound of step (f) in dichloromethane, triethylamine, acetic anhydride and 4-Dimethylaminopyridine for the time period ranging from 3 to 4 that the temperature ranging from 25 C. to 30 C. to obtain (S)-2-(1,5,5-trimethylcyclopent-2-en-1-yl) ethyl acetate.

[0062] The enantiospecific process for preparation of (S)-(+)-pheromone of the long-tailed mealybug is as shown in scheme 4 below:

##STR00009##

[0063] In another embodiment, the present invention provides novel intermediates which are useful for preparation of enantiomers of sex pheromones of the long-tailed mealybug.

[0064] In preferred embodiments, said novel intermediates are selected from (3aS,5S,6aR)-5-hydroxy-3a,4,4-trimethylhexahydro-2H-cyclopenta[b]furan-2-one, (3aS,6aR)-3a,4,4-trimethyltetrahydro-2H-cyclopenta[b]furan-2,5(3H)-dione, methyl-2-(1,5,5-trimethyl-4-oxocyclopent-2-en-1-yl)acetate, methyl 2-((1R)-4-hydroxy-1,5,5-trimethylcyclopent-2-en-1-yl)acetate, methyl 2-(1,5,5-trimethylcyclopent-2-en-1-yl)acetate, 2-(1,5,5-trimethylcyclopent-2-en-1-yl)ethan-1-ol.

[0065] The following examples, which include preferred embodiments, will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpose of illustrative discussion of preferred embodiments of the invention.

EXAMPLES

Example 1: Synthesis of (3aS,5S,6aR)-5-hydroxy-3a,4,4-trimethylhexahydro-2H-cyclopenta[b]furan-2-one (()-3)

[0066] ##STR00010##

[0067] Acetic acid (6 mL), H.sub.2O.sub.2 (35 wt % in water, 5 mL) and H.sub.2SO.sub.4 (1 mL) was taken in an RB to which ()-2 (1.9 g, 9.03 mmol) was added and stirred at room temperature for 24 h. Ethyl acetate was added and the aqueous layers was extracted thrice. The organic layer was dried and the solvent was evaporated under reduced pressure. The crude thus obtained was dissolved in methanol, added K.sub.2CO.sub.3 and stirred at room temperature for 3 h. The reaction mixture was passed through celite and the filtrate was concentrated and purified by column chromatography (230-400 silica gel) using 25-30% Ethylacetate-pet ether to afford the product as a colorless crystalline solid (832 mg, 50%). The structure was unambiguously confirmed by X-ray crystal structure analysis. Mp=224-226 C.; [].sub.D.sup.29=9.2 (c=0.33); .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 4.54 (d, J=8.6 Hz, 1H), 3.90 (d, J=5.1 Hz, 1H), 3.34 (d, J=18.1 Hz, 1H), 2.54-2.46 (m, 1H), 2.06 (d, J=18.1 Hz, 1H), 1.86 (d, J=15.9 Hz, 1H), 1.13 (s, 3H), 1.03 (s, 3H), 0.84 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) ppm 177.8, 90.5, 81.4, 50.71, 46.5, 40.2, 39.8, 24.2, 22.2, 18.3; IR .sub.max (thin film applied as CHCl.sub.3 solution) 3470 (broad peak), 2969, 1764, 1069 cm.sup.1; HRMS (ESI): m/z calculated for C.sub.10H.sub.16O.sub.3Na [M+Na]+207.0992, found 207.0985.

[0068] A. X-Ray Crystal Structure Details of ()-3:

[0069] Single crystals of compound ()-3 was obtained from chloroform. X-ray intensity data were collected on a APEX II CCD diffractometer with graphite-monochromatized (Mo K=0.71073 ) radiation at room temperature 296(2) K. The X-ray generator was operated at 50 kV and 30 mA. Diffraction data were collected with a scan width of 0.5 and at different settings of and 2. The sample-to-detector distance was fixed at 5.00 cm. The X-ray data acquisition was monitored by APEX II program suite..sup.14 All the data were corrected for Lorentz-polarization and absorption effects using SAINT and SADABS programs integrated in APEX II program package..sup.14 The structures were solved by direct method and refined by full matrix least squares, based on F.sup.2, using SHELX-97..sup.15 ORTEP diagrams was generated using XSHELL program integrated in SHELXTL package.sup.15 with 30% probability displacement ellipsoids and H atoms are shown as small spheres of arbitrary radii. All the H-atoms were placed in geometrically idealized position (CH=0.97 for the methylene H-atom, CH=0.96 for the methyl H-atom, CH=0.98 for the methine H-atom and OH=0.82 for the hydroxyl H-atom) and constrained to ride on their parent atoms [U.sub.iso(H)=1.2 U.sub.eq(C) for the methylene and methine group, U.sub.iso(H)=1.5 U.sub.eq(C) for the methyl group and U.sub.iso(H)=1.5 U.sub.eq(0) for the hydroxyl group].

[0070] B. Crystallographic data for ()-3:

[0071] (C.sub.10H.sub.16O.sub.3): M=184.23, Crystal dimensions 0.640.600.20 mm.sup.3, orthorhombic, space group P2.sub.12.sub.12.sub.1, a=6.9872(7), b=11.6575(12), c=11.8586(12) , V=965.92(17) .sup.3, Z.sup.=4, .sub.calcd=1.267 gcm.sup.3, (Mo-K.sub.)=0.092 mm.sup.1, F(000)=400, 2.sub.max=50.000, T=296(2) K, 5178 reflections collected, 1648 unique, 1532 observed (I>2 (I)) reflections, 122 refined parameters, R value 0.0329, wR2=0.0806, (all data R=0.0356, wR2=0.0824), S=1.091, minimum and maximum transmission 0.943 and 0.982; maximum and minimum residual electron densities +0.09 and 0.11 e .sup.3.

Example 2: Synthesis of (3aS,6aR)-3a,4,4-trimethyltetrahydro-2H-cyclopenta[b]furan-2,5(3H)-dione (()-4)

[0072] ##STR00011##

[0073] To a solution of ()-3 (1.2 g, 6.5 mmol) in dry DCM, molecular sieves was added followed by PDC (3.7 g, 9.8 mmol) and stirred at room temperature for overnight. The reaction mass was filtered through celite. The filtrate was washed with 1N HCl, dried and concentrated. The crude mass was purified by column chromatography (100-200 silica gel) using 15% ethyl acetate-pet ether to give the compound as a white crystalline solid (1.05 g, 89% yield). Mp=169-171 C.; [].sub.D.sup.29=98.28 (c=0.32); .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 4.79 (dd, J=9.0, 4.2 Hz, 1H), 3.02 (dd, J=20.3, 8.8 Hz, 1H), 2.44 (dd, J=20.3, 4.2 Hz, 1H), 2.32 (AB quartet, 2H), 1.27 (s, 3H), 1.08 (s, 3H), 1.02 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) ppm 216.3, 175.3, 82.7, 52.4, 50.1, 41.1, 39.0, 21.2, 19.3, 18.8; IR .sub.max (thin film applied as CHCl.sub.3 solution) 2973, 2884, 1783, 1747, 1460, 1288, 1177, 1050 cm.sup.1; HRMS (ESI): m/z calculated for C.sub.10H.sub.15O.sub.3[M+H].sup.+ 183.1016, found 183.1011.

Example 3: Synthesis of methyl (R)-2-(1,5,5-trimethyl-4-oxocydopent-2-en-1-yl)acetate (()-5)

[0074] ##STR00012##

[0075] The compound ()-4 was dissolved in dry methanol, PTSA was added and refluxed at 65 C. for 24 h. The reaction mass was cooled and solvent was removed under reduced pressure. Water and DCM was added and the organic layer was separated, aqueous layer was extracted with DCM and the combined organics were dried and concentrated under reduced pressure. The pure product was obtained by column chromatography (silica gel 100-200) using 10% ethyl acetate-petether to afford the product as a colourless liquid (475 mg, 88% yield) along with recovery of starting material (30 mg). [].sub.D.sup.29=4.45 (c=0.34); .sup.1H NMR (500 MHz, CDCl.sub.3) ppm 7.71 (d, J=5.8 Hz, 1H), 6.08 (d, J=5.8 Hz, 1H), 3.71 (s, 3H), 2.51 (d, J=14.9 Hz, 1H), 2.39 (d, J=14.9 Hz, 1H), 1.18 (s, 3H), 1.09 (s, 3H), 1.06 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) ppm 213.5, 171.9, 168.5, 129.0, 51.6, 51.3, 48.5, 41.5, 23.0, 22.7, 20.9; IR .sub.max (thin film applied as CHCl.sub.3 solution) 2969, 2883, 1715, 1594, 1203 cm.sup.1; HRMS (ESI): m/z calculated for C.sub.11H.sub.17O.sub.3 [M+H].sup.+ 197.1172, found 197.1173.

Example 4: Synthesis of methyl 2-((1R)-4-hydroxy-1,5,5-trimethylcyclopent-2-en-1-yl)acetate (6)

[0076] ##STR00013##

[0077] A solution of ()-5 (200 mg, 1.02 mmol) in dry methanol was cooled to 0 C., added CeCl.sub.3.7H.sub.2O (418 mg, 1.12 mmol), followed by sodiumborohydride (77 mg, 2.04 mmol) and stirred at room temperature for 1 h. The reaction mass was cooled to 0 C., quenched with sat. NH.sub.4Cl and methanol was removed in rotary evaporator. Ethyl acetate was added and the aqueous layer was extracted, dried over Na.sub.2SO.sub.4 and concentrated to give the product as a colourless liquid (200 mg, quantitative). Data for major diastereomer: .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 5.98 (d, J=5.6 Hz, 1H), 5.78-5.74 (m, 1H), 4.27 (d, J=13.2 Hz, 1H), 3.66 (s, 3H), 2.40 (AB quartet, 2H), 1.00 (s, 3H), 0.96 (s, 3H), 0.93 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) ppm 173.2, 141.8, 130.6, 84.4, 51.3, 49.6, 47.3, 43.4, 23.6, 20.2, 17.8.

Example 5: Synthesis of methyl (R)-2-(1,5,5-trimethylcyclopent-2-en-1-yl)acetate

[0078] ##STR00014##

[0079] A solution of 6 (70 mg, 0.353 mmol) in dry THF was cooled to 0 C., added BF.sub.3.Et.sub.2O (0.13 mL, 1.059 mmol) followed by sodiumcyanoborohydride (66 mg, 1.059 mmol) and refluxed at 66 C. for overnight. The reaction was quenched with 2N NaOH, added DCM and the organic layer was separated. It was then dried, concentrated and purified by column chromatography (silica gel 230-400 gel) using 2% ethyl acetate-petether to give the product as a mixture with its regioisomer (55 mg, 86% combined yield, 10:3 ratio by NMR). Data for major isomer: .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 5.80-5.76 (m, 1H), 5.68-5.65 (m, 1H), 3.68 (s, 3H), 2.44-2.07 (m, 4H), 0.99 (s, 6H), 0.96 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) ppm 173.6, 138.7, 127.9, 51.2, 49.8, 46.7, 44.1, 40.6, 24.4, 24.0, 19.8.

Example 6: Synthesis of (R)-2-(1,5,5-trimethylcyclopent-2-en-1-yl)ethan-1-ol (()-(7a)

[0080] ##STR00015##

[0081] The regioisomeric mixture obtained in the above step was used to prepare the title compound. The compound (50 mg, 0.275 mmol) was dissolved in dry THF, cooled to 0 C., added LAH (31 mg, 0.824 mmol) and stirred at room temperature for 2 h. The reaction mixture was quenched with saturated Na.sub.2SO.sub.4, ethyl acetate was added and the organic layer was separated, dried and purified by column chromatography (silica gel 230-400 mesh) using 5% ethyl acetate-petether to give the product as a colourless liquid (40 mg, 95% along with its regioisomer). Both the regioisomers could be separated by flash column chromatography although they were inseparable in TLC. [].sub.D.sup.26=10.36 (c=1.14); .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 5.65-5.63 (m, 1H), 5.59-5.57 (m, 1H), 3.81-3.68 (m, 2H), 2.15-2.13 (m, 2H), 1.73-1.65 (m, 1H), 1.59-1.52 (m, 1H), 0.97 (s, 3H), 0.95 (s, 3H), 0.90 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) ppm 139.1, 128.0, 60.8, 49.5, 46.8, 44.0, 39.2, 24.8, 23.9, 19.4; HRMS (ESI): m/z calculated for C.sub.10H.sub.19O [M+H].sup.+ 155.1435, found 155.1430.

Example 7: Synthesis of (S)-2-(1,2,2-Trimethylcydopent-3-en-1-yl)ethan-1-ol((+)-7b)

[0082] ##STR00016##

[0083] [].sub.D.sup.25+14.5 (c 0.17, CHCl.sub.3); .sup.1H NMR (500 MHz, CDCl.sub.3) ppm 5.54-5.51 (m, 1H), 5.44-5.43 (m, 1H), 3.79-3.64 (m, 2H), 2.32-2.28 (m, 1H), 2.03-2.00 (m, 1H), 1.73-1.60 (m, 2H), 0.92 (s, 3H), 0.90 (s, 3H), 0.90 (s, 3H).

Example 7: Synthesis of (R)-2-(1,5,5-trimethylcydopent-2-en-1-yl) ethyl acetate

[0084] ##STR00017##

[0085] To a solution of ()-7a (10 mg, 0.065 mmol) in dry DCM, triethylamine (36 L, 0.26 mmol) and acetic anhydride (12 L, 0.13 mmol) was added followed by a pinch of DMAP and stirred at room temperature for 3 h. Water was added and the organic layer was separated, dried, concentrated and purified by column chromatography (100-200 silica gel) using 20% DCM-pentane to afford the product as a colourless liquid (11 mg, 86%). [o]D.sup.25-20.6 (c 0.33, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 5.66-5.63 (m, 1H), 5.58-5.56 (m, 1H), 4.24-4.07 (m, 2H), 2.14 (t, J=2.2 Hz, 2H), 2.06 (s, 3H), 1.75-1.68 (m, 1H), 1.63-1.54 (m, 1H, merged with moisture peak), 0.97 (s, 3H), 0.96 (s, 3H), 0.91 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) ppm 171.2, 138.7, 128.2, 62.8, 49.4, 46.8, 44.0, 34.5, 24.6, 24.0, 21.1, 19.4; HRMS (ESI): m/z calculated for C.sub.12H.sub.20O.sub.2Na [M+Na].sup.+ 219.1356, found 219.1355.

Example 8: Synthesis of (S)-(+)-pheromone

[0086] The same route was followed for the synthesis of the other antipode (S)-(+)-pheromone starting from (+)-2. The NMR data of all the compounds were found to be exactly matching. The optical rotations also showed the same magnitude but with an inverse sign. The data of known compounds were compared with literature reports and found to be identical.

Example 9: Synthesis of (3aR,5R,6aS)-5-Hydroxy-3a,4,4-trimethylhexahydro-2H-cyclopenta[b]furan-2-one (+)-3

[0087] Yield: 48%; [].sub.D.sup.28+6.8 (c 0.34, CHCl.sub.3)

Example 10: Synthesis of (3aR,6aS)-3a,4,4-Trimethyltetrahydro-2H-cyclopenta[b]furan-2,5(3H)-dione (+)-4

[0088] Yield: 95%; [].sub.D.sup.28+98.3 (c 0.27, CHCl.sub.3)

Example 11: Synthesis of Methyl(S)-2-(1,5,5-trimethyl-4-oxocydopent-2-en-1-yl)acetate (+)-5

[0089] Yield: 80%, 97% brsm; [].sub.D.sup.25+4.5 (c 0.50, CHCl.sub.3)

Example 12: Synthesis of (S)-2-(1,5,5-Trimethylcyclopent-2-en-1-yl)ethan-1-ol ((+)-7a)

[0090] [].sub.D.sup.26+11.3 (c 0.30, CHCl.sub.3)

Example 13: Synthesis of (R)-2-(1,2,2-Trimethylcydopent-3-en-1-yl)ethan-1-ol(()-7b)

[0091] [].sub.D.sup.24-13.8 (c 0.17, CHCl.sub.3); .sup.1H NMR (400 MHz, CDCl.sub.3) ppm 5.54-5.51 (m, 1H), 5.44-5.43 (m, 1H), 3.79-3.64 (m, 2H), 2.32-2.28 (m, 1H), 2.03-1.98 (m, 1H), 1.73-1.60 (m, 2H), 0.91 (s, 3H), 0.90 (s, 3H), 0.89 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) ppm 141.6, 126.2, 61.1, 48.7, 44.9, 44.7, 39.6, 23.8, 22.3, 22.2.

Example 14: Synthesis of (S)-2-(1,5,5-Trimethylcydopent-2-en-1-yl)ethyl acetate

[0092] Yield: 94%; [o].sub.D.sup.32+23.7 (c 0.33, CHCl.sub.3)

ADVANTAGES OF INVENTION

[0093] Useful in the field of agriculture to improve the quantitative and qualitative production. [0094] Useful in crop protection and may help in protecting high value crops such as grapes, citrus, apples, pears, pomegranate, cotton and ornamental plants.