Concise synthesis and biological activities of 2α-Alkyl- and 2α-(ω-Hydroxyalkyl)-20-epi-1α,25-dihydroxyvitamin D3

We found a concise route to the Trost A-ring precursor enyne for synthesizing 2α-alkylated 1α,25-dihydroxyvitamin D3 (1) from -glucose. The enynes were coupled with the 20-epi-CD ring part to study the effect of the double modification of 2α-substitution and 20-epimerization upon biological activities of 1. The novel three analogues of 2α-alkyl- and four analogues of 2α-(ω-hydroxyalkyl)-20-epi-1α,25-dihydroxyvitamin D3 (5b–d and 6a–d) showed higher binding affinity for vitamin D receptor (VDR) and more potent activity in induction of HL-60 cell differentiation than those of the natural hormone 1.