Synthesis of 2-methyl and ethyl-substituted 19-nor-1α,25-dihydroxyvitamin D3 analogues via the cyclovitamin strategy

The synthesis of several 19-nor-2-alkyl-1 alpha,25-dihydroxyvitamin D-3 analogues (5-14) is described following the cyclovitamin strategy. Starting from all-cis methyl 3,5-dihydroxy-4alkyl-1-cyclohexanecarboxylate (29), the eight stereoisomeric A-ring-precursor 2-tert-butyldiphenylsilyloxy-3 alpha-formyl-1-alkylbicyclo[3.1.0]hexanes (39, 44, 46, 63, 65, 67, 69, 71) were prepared in two series: a (R = methyl) and b (R = ethyl). In particular, from the coupling of 39 and the lithiated compounds derived from the CD-ring bromides 20 and 21 possessing the natural or the 23-yne side chain, the title derivatives 5-14 were synthesized. (c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)