Synthesis and biological activity of 2α-hydroxyvitamin D3

Abstract

From 2α-hydroxycholesterol, obtained by hydroboration–oxidation of cholesta-1,5-dien-3β-ol, the 2α-hydroxylated analogue of cholesta-5,7-dien-3β-ol (provitamin D) has been prepared via the usual four-step procedure: (i) acetylation, (ii) bromination, (iii) dehydrobromination, and (iv) hydrolysis. 2α-Hydroxycholecalciferol (2α-OH-D₃), produced by irradiation of cholesta-5,7-dien-2α,3β-diol, did not show any significant biological activity on bone and intestine in rats, suggesting that the 2α-hydroxy-function does not mimic (at least significantly) the 1α-hydroxy-function. Vitamin D₃ itself was much more potent than 2α-OH-D₃ in inducing calcium transport activity. The presence of the 2α-hydroxy-function seems to be inhibitory to the metabolism of vitamin D₃.