合成路线1

The condensation of intermediates (VII) and (XIII) by means of n-BuLi in THF, followed by hydrogenation, with H2 over Pd/C in ethyl acetate gives the protected ketone (XIV). The deprotection of the two Tes groups of (XIV) with CSA in chloroform/methanol gives rise to simultaneous intramolecular ketalization to give the two 6,6-spiroketals (XV) and (XVI) with opposite stereochemistry at the spiro center, which are separated by conventional methods. Spiroketal (XV), with correct stereochemistry, is treated with MeI and NaHCO3 in acetone/water to eliminate the mtm protecting group, and the resulting alcohol is esterified with monoallyl succinate (XVII) by means of DCC and DMAP in dichloromethane, yielding the ester (XVIII). The desilylation of (XVIII) with HF in pyridine/THF, followed by oxidation of the resulting alcohol with DMP, affords the aldehyde (XX), which is condensed with phosphonate (XXII) by means of LHMDS and HMPA in THF to give unsaturated allyl ester (XXIII). Elimination of the mpm protecting group of (XXIII) with DDQ in dichloromethane affords the primary alcohol (XXV). Spiroketal (XVI), with opposite stereochemistry, can be recovered by submitting it to the same sequence of reactions as (XV) to furnish intermediates (XIX), (XXI), (XXIV) and finally (XXVI), which is isomerized to (XXV) by treatment with CSA in chloroform/methanol.