Potential Intermediates to Vitamin D₃ and Steroids : Enantioselective Syntheses of (20R)- and (20S)-De-AB-cholesta-8(14), 22-dien-9-one from (S)- and (R)-2, 3-O-Isopropylideneglyceraldehyde

Abstract

Enantioselective syntheses of both (20R)- and (20S)-de-AB-cholesta-8(14), 22-dien-9-one (22 and 23), which are potential intermediates leading to vitamin D₃, steroids and their analogues, have been developed. The (3R)-methyl-cyclopentanone 12 was obtained through a known procedure starting with (S)-2, 3-O-isopropylideneglyceraldehyde (8) or through inversion of the C₆ position in compound 5 using the Mitsunobu reaction followed by orthoester Claisen rearrangement. The construction of the trans-angularly methylated CD ring was accomplished through stereo- and regioselective Michael addition of the lithium enolate of 12 to α-silylated vinyl ketone, followed by intramolecular aldol condensation.