Synthetic and structural studies of key intermediates toward forskolin and/or erigerol. Relative stereochemistry, conformational preferences and stereoselectivity control

Abstract

An alternative stereoselective synthesis of compound 9c, an intermediate in the synthesis of the highly oxygenated diterpene erigerol 2, was accomplished through an organometallic addition to the α,β-unsaturated ketone 7, followed by osmylation and protection of the resultant diol. In spite of the fact that the addition of the Iithio derivative of N,S-dimethyl-S-phenylsulfoximide occurred exclusively from the β face of enone 7, this approach to the alcohol 8c, a key intermediate toward forskolin 1, is not suitable because of the low yield of the osmylation step. With the aid of one- and two-dimensional NMR techniques and a series of NOE experiments, the complete stereochemistry and conformational preferences of alcohols 8a, 8c, 9a and 9c were established. The lowest-energy conformations of alcohols 8a, 8c and 9c, based on molecular mechanics calculations, confirmed the results obtained by NMR spectroscopy.