Structural analogs of lα,25-dihydroxycholecalciferol: Preparation and biologial assay of 1α-hydroxypregnacalciferol

Abstract

The synthesis of lα-hydroxypregnacalciferol, a side chain analog of lα,25-dihydroxycholecalciferol (1α,25-dihydroxyvitamin D 3), is described. Pregnenolone acetate was converted in five steps to 5-pregnen-lα,3β-diol. Conversion of the diol to pregna-5,7-diene-lα,3β diol diacetate followed by ultraviolet irradiation gave the corresponding provitamin derivative. Thermal isomerization, hydrolysis and chromatography then furnished the desired analog, lα-hydroxypregnacalciferol. The compound was tested in vivo for its effect on intestinal calcium transport, serum calcium and phosphate levels and bone calcification, and in vitro for its effect on bone resorption. When given to intact rats, either as a single dose or in repeated daily doses, the analog even at high dose levels, exhibited no biological activity. The compound stimulated bone resorption in vitro , but only at high concentrations.