SYNTHETIC AND STRUCTURAL STUDIES OF KEY INTERMEDIATES TOWARD FORSKOLIN AND OR ERIGEROL - RELATIVE STEREOCHEMISTRY, CONFORMATIONAL PREFERENCES AND STEREOSELECTIVITY CONTROL

An alternative stereoselective synthesis of compound 9c, an intermedia te in the synthesis of the highly oxygenated diterpene erigerol 2, was accomplished through an organometallic addition to the alpha,beta-uns aturated ketone 7, followed by osmylation and protection of the result ant diol. In spite of the fact that the addition of the lithio derivat ive of N,S-dimethyl-S-phenylsulfoximide occurred exclusively from the beta face of enone 7, this approach to the alcohol 8c, a key intermedi ate toward forskolin 1, is not suitable because of the low yield of th e osmylation step. With the aid of one- and two-dimensional NMR techni ques and a series of NOE experiments, the complete stereochemistry and conformational preferences of alcohols 8a, 8c, 9a and 9c were establi shed. The lowest-energy conformations of alcohols 8a, 8c and 9c, based on molecular mechanics calculations, confirmed the results obtained b y NMR spectroscopy.