A novel and practical route to A-ring enyne synthon for 1α,25-dihydroxyvitamin D3 analogs:: Synthesis of A-Ring diastereomers of 1α,25-dihydroxyvitamin D3 AND 2-methyl-1,25-dihydroxyvitamin D3

A novel and practical route to the A-ring enyne synthon (2), which can be versatile for a variety of A-ring analogs of 1 alpha,25-dihydroxyvitamin D-3 (1), was developed. This novel method led to an improved synthesis of the A-ring diastereomers of 1, the compounds 13-15, and synthesis of the new analogs, 2-methyl-1,25-dihydroxyvitamin D-3 (4) with its all possible diastereomers. The biological evaluation of the 2-methyl analogs showed the alpha alpha beta-isomer to be more potent than 1. (C) 1998 Elsevier Science Ltd. All rights reserved.