The Wittig condensation of cis-bicyclo[4.3.0]nona-3-en-8-one (I) with triethyl phosphonoacetate (II) by means of NaH in THF gives 2-(cis-bicyclo[4.3.0]octa-3-en-8-ylidene)acetic acid ethyl ester (III), which is reduced with Li in liquid ammonia to the corresponding ethanol derivative (IV). The condensation of (IV) with N-benzyl-2-chloro-N-phenylacetamide (V) by means of NaH in toluene affords the corresponding ethoxyacetamide (VI), which is treated with ozone in methanol to give the epoxide (VII). Cleavage of (VII) with dimethyl sulfide in the same solvent yields the dialdehyde (VIII), which is submitted to an aldol cyclization by means of NaOH in methanol/water to afford the 2beta-formyl-3alpha-hydroxy derivative (IX). The Wittig condensation of aldehyde (IX) with dimethyl 4(S)-methyl-2-oxooctylphosphonate (X) by means of NaH in THF gives the unsaturated hydroxy ketone (XI). The ketone group of (XI) is reduced with NaBH4 in methanol, and the resulting diastereomeric diols obtained are separated by column chromatography to yield the alpha,alpha-dihydroxy compound (XII). The hydrolysis of (XII) with KOH in refluxing ethanol/water yields the corresponding free acid (XIII), which is finally methylated with diazomethane in ethyl ether to obtain a mixture of the epoxy alcohol (XXIVa) and the unsaturated alcohol (XXIVb). A chromatographic separation of the mixture followed by desilylation with acetic acid in methanol gives the desired final product.

The reduction of the enone (I) with Red Al or NaBH4 gives the corresponding alcohol (XIV), which is mesylated with methanesulfonyl chloride to the ester (XV). The condensation of (XV) with dimethyl malonate by means of NaH in toluene/methanol yields the malonic derivative (XVI), which is submitted to hydrolysis with KOH and partial decarboxylation in refluxing toluene to afford the substituted acetic acid (XVII). This compound is then reduced with Red Al or LiAlH4 to the ethanol derivative (IV), already obtained. The condensation of (IV) with sodium chloroacetate by means of BuLi in DMSO, followed by esterification with methanol in H2SO4 gives the ethoxyacetic ester (XVIII), which is treated with H2O2 and Na2WO4 in dichloromethane/water with a phase-transfer agent in order to obtain the epoxide (XIX). The cleavage of (XIX) with HIO4 in the same solvent mixture affords the dialdehyde (XX), which is submitted to an aldol condensation by means of piperidine/acetic acid, yielding a mixture of two hydroxy aldehydes (XXIa and XXIb). This mixture is submitted to a Wittig condensation with the phosphonate (X), already used, and a mixture of two isomeric hydroxy ketones (XXIIa and XXIIb) is obtained. The free hydroxy group of (XXIIa and XXIIb) is protected with tert-butyldimethylsilyl chloride, and then the oxo group is reduced with NaBH4 and CeCl3 to obtain the mixture of unsaturated alcohols (XXIIIa and XXIIIb).

This new mixture is submitted to a selective epoxidation with (-)-DIPT, titanium tetraisopropoxide and TBHP in order to obtain a mixture of the epoxy alcohol (XXIVa) and the unsaturated alcohol (XXIVb). A chromatographic separation of the mixture followed by desilylation with acetic acid in methanol gives the desired final product.

This new mixture is submitted to a selective epoxidation with (-)-DIPT, titanium tetraisopropoxide and TBHP in order to obtain a mixture of the epoxy alcohol (XXIVa) and the unsaturated alcohol (XXIVb). A chromatographic separation of the mixture followed by desilylation with acetic acid in methanol gives the desired final product.

This new mixture is submitted to a selective epoxidation with (-)-DIPT, titanium tetraisopropoxide and TBHP in order to obtain a mixture of the epoxy alcohol (XXIVa) and the unsaturated alcohol (XXIVb). A chromatographic separation of the mixture followed by desilylation with acetic acid in methanol gives the desired final product.

The reduction of the enone (I) with Red Al or NaBH4 gives the corresponding alcohol (XIV), which is mesylated with methanesulfonyl chloride to the ester (XV). The condensation of (XV) with dimethyl malonate by means of NaH in toluene/methanol yields the malonic derivative (XVI), which is submitted to hydrolysis with KOH and partial decarboxylation in refluxing toluene to afford the substituted acetic acid (XVII). This compound is then reduced with Red Al or LiAlH4 to the ethanol derivative (IV), already obtained. The condensation of (IV) with sodium chloroacetate by means of BuLi in DMSO, followed by esterification with methanol in H2SO4 gives the ethoxyacetic ester (XVIII), which is treated with H2O2 and Na2WO4 in dichloromethane/water with a phase-transfer agent in order to obtain the epoxide (XIX). The cleavage of (XIX) with HIO4 in the same solvent mixture affords the dialdehyde (XX), which is submitted to an aldol condensation by means of piperidine/acetic acid, yielding a mixture of two hydroxy aldehydes (XXIa and XXIb). This mixture is submitted to a Wittig condensation with the phosphonate (X), already used, and a mixture of two isomeric hydroxy ketones (XXIIa and XXIIb) is obtained. The free hydroxy group of (XXIIa and XXIIb) is protected with tert-butyldimethylsilyl chloride, and then the oxo group is reduced with NaBH4 and CeCl3 to obtain the mixture of unsaturated alcohols (XXIIIa and XXIIIb).

This new mixture is submitted to a selective epoxidation with (-)-DIPT, titanium tetraisopropoxide and TBHP in order to obtain a mixture of the epoxy alcohol (XXIVa) and the unsaturated alcohol (XXIVb). A chromatographic separation of the mixture followed by desilylation with acetic acid in methanol gives the desired final product.

The Wittig condensation of cis-bicyclo[4.3.0]nona-3-en-8-one (I) with triethyl phosphonoacetate (II) by means of NaH in THF gives 2-(cis-bicyclo[4.3.0]octa-3-en-8-ylidene)acetic acid ethyl ester (III), which is reduced with Li in liquid ammonia to the corresponding ethanol derivative (IV). The condensation of (IV) with N-benzyl-2-chloro-N-phenylacetamide (V) by means of NaH in toluene affords the corresponding ethoxyacetamide (VI), which is treated with ozone in methanol to give the epoxide (VII). Cleavage of (VII) with dimethyl sulfide in the same solvent yields the dialdehyde (VIII), which is submitted to an aldol cyclization by means of NaOH in methanol/water to afford the 2beta-formyl-3alpha-hydroxy derivative (IX). The Wittig condensation of aldehyde (IX) with dimethyl 4(S)-methyl-2-oxooctylphosphonate (X) by means of NaH in THF gives the unsaturated hydroxy ketone (XI). The ketone group of (XI) is reduced with NaBH4 in methanol, and the resulting diastereomeric diols obtained are separated by column chromatography to yield the alpha,alpha-dihydroxy compound (XII). The hydrolysis of (XII) with KOH in refluxing ethanol/water yields the corresponding free acid (XIII), which is finally methylated with diazomethane in ethyl ether to obtain a mixture of the epoxy alcohol (XXIVa) and the unsaturated alcohol (XXIVb). A chromatographic separation of the mixture followed by desilylation with acetic acid in methanol gives the desired final product.

The reduction of the enone (I) with Red Al or NaBH4 gives the corresponding alcohol (XIV), which is mesylated with methanesulfonyl chloride to the ester (XV). The condensation of (XV) with dimethyl malonate by means of NaH in toluene/methanol yields the malonic derivative (XVI), which is submitted to hydrolysis with KOH and partial decarboxylation in refluxing toluene to afford the substituted acetic acid (XVII). This compound is then reduced with Red Al or LiAlH4 to the ethanol derivative (IV), already obtained. The condensation of (IV) with sodium chloroacetate by means of BuLi in DMSO, followed by esterification with methanol in H2SO4 gives the ethoxyacetic ester (XVIII), which is treated with H2O2 and Na2WO4 in dichloromethane/water with a phase-transfer agent in order to obtain the epoxide (XIX). The cleavage of (XIX) with HIO4 in the same solvent mixture affords the dialdehyde (XX), which is submitted to an aldol condensation by means of piperidine/acetic acid, yielding a mixture of two hydroxy aldehydes (XXIa and XXIb). This mixture is submitted to a Wittig condensation with the phosphonate (X), already used, and a mixture of two isomeric hydroxy ketones (XXIIa and XXIIb) is obtained. The free hydroxy group of (XXIIa and XXIIb) is protected with tert-butyldimethylsilyl chloride, and then the oxo group is reduced with NaBH4 and CeCl3 to obtain the mixture of unsaturated alcohols (XXIIIa and XXIIIb).

This new mixture is submitted to a selective epoxidation with (-)-DIPT, titanium tetraisopropoxide and TBHP in order to obtain a mixture of the epoxy alcohol (XXIVa) and the unsaturated alcohol (XXIVb). A chromatographic separation of the mixture followed by desilylation with acetic acid in methanol gives the desired final product.