合成路线1

The reduction of the protected (S)-ethyl lactate (I) with DIBAL in dichloromethane gives the aldehyde (II), which by a Grignard condensation with allylmagnesium bromide (III) in ethyl ether yields the homoallylic alcohol (IV). The reaction of (IV) with Tbdms-Cl and imidazole in DMF affords the silyl ether (V), which is ozonolyzed with O3 in dichloromethane/methanol to provide the aldehyde (VI), which, by a new Grignard condensation with isopropenylmagnesium bromide (VII) in THF, gives the allyl alcohol derivative (VIII). Compound (VIII) is treated with triethyl orthoacetate (refluxing xylene) in a Johnson Claisen rearrangement to yield the (E)-unsaturated ester (IX), which is debenzylated by treatment with DDQ to afford the secondary alcohol (X). The oxidation of (X) with oxalyl chloride provides the ketoester (XI), which is oxidized with AD-mix beta in tert-butanol/water to furnish the diol (XII) as an inseparable mixture of isomers. This mixture, by a Wittig condensation with the phosphonium salt (XIII) and KHMDS in THF, gives a mixture of the hydroxylactones (XIV) and (XV) that are separated by chromatography. Compound (XIV) is mesylated with MsCl and TEA and treated with K2CO3 in methanol to give the desired epoxyester (XVI). The diastereomer (XV) with wrong configuration is recovered by a double inversion: Compound (XV) is mesylated and the resulting derivative is then epoxidated with K2CO3 in methanol to yield the epoxide (XVII), which is treated with K2CO3 in methanol/water to afford the hydroxylactone (XIV) with the adequate configuration.