Structural analogs of 1alpha,25-dihydroxycholecalciferol: preparation and biological assay of 1alpha-hydroxypregnacalciferol.
The synthesis of 1alpha-hydroxypregnacalciferol, a side chain analog of 1alpha,25-dihydroxycholecalciferol (1alpha,25-dihydroxyvitamin D3), is described. Pregnenolone acetate was converted in five steps to 5-pregnen-1alpha,3beta-diol. Conversion of the diol to pregna-5,7-diene-1alpha,3beta diol diacetate followed by ultraviolet irradiation gave the corresponding previtamin derivative. Thermal isomerization, hydrolysis and chromatography then furnished the desired analog, 1alpha-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.
D000818:Animals; D001681:Biological Assay; D001693:Biological Transport, Active; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D004100:Dihydroxycholecalciferols / Q000138:chemical synthesis / Q000494:pharmacology*; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D008722:Methods; D010710:Phosphates / Q000097:blood; D051381:Rats; D013329:Structure-Activity Relationship; D014808:Vitamin D Deficiency / Q000378:metabolism
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D010710:Phosphates; D002118:Calcium