Synthesis of 2‐Methyl and Ethyl‐Substituted 19‐ nor ‐1α,25‐Dihydroxyvitamin D 3 Analogues via the Cyclovitamin Strategy

The synthesis of several 19‐ nor ‐2‐alkyl‐1α,25‐dihydroxyvitamin D 3 analogues ( 5 – 14 ) is described following the cyclovitamin strategy. Starting from all ‐ cis methyl 3,5‐dihydroxy‐4‐alkyl‐1‐cyclohexanecarboxylate ( 29 ), the eight stereoisomeric A‐ring‐precursor 2‐ tert ‐butyldiphenylsilyloxy‐3α‐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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)