Concise synthesis and biological activities of 2alpha-alkyl- and 2alpha-(omega-hydroxyalkyl)-20-epi-1alpha,25-dihydroxyvitamin D3.
We found a concise route to the Trost A-ring precursor enyne for synthesizing 2alpha-alkylated 1alpha,25-dihydroxyvitamin D(3) (1) from D-glucose. The enynes were coupled with the 20-epi-CD ring part to study the effect of the double modification of 2alpha-substitution and 20-epimerization upon biological activities of 1. The novel three analogues of 2alpha-alkyl- and four analogues of 2alpha-(omega-hydroxyalkyl)-20-epi-1alpha,25-dihydroxyvitamin D(3) (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.
D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans
D002117:Calcitriol