Synthesis and biological activity of 25xi,26-dihydroxycholecalciferol.
25xi,26-Dihydroxycholecalciferol (25xi,26-dihydroxyvitamin D3), a metabolite of vitamin D3 preferentially active on intestine has been synthesized. This compound was prepared by converting 3beta-hydroxy-27-norcholest-5-en-25-one to 25xi,26-epoxy-5-cholesten--3beta-ol and base-catalyzed hydrolysis of the latter to 5-cholestene-3beta,25xi,26-triol; allylic bromination of the corresponding triacetate, and dehydrobromination gave the required 5,7-diene which yielded the vitamin derivative upon photolysis (Figure 3). The synthetic product shows the same activity pattern as the natural metabolite: at dose levels of 0.25 mug, the compound stimulates intestinal calcium transport, but has no effect on bone calcium mobilization in rats maintained on a vitamin D-deficient, low calcium diet. Higher doses (2.5 mug) elicit a more pronounced intestinal calcium transport response, but also have no significant effect on the bone mobilization system. The compound exhibits no biologial activity in nephrectomized animals.
D000818:Animals; D001681:Biological Assay; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism; D004100:Dihydroxycholecalciferols / Q000138:chemical synthesis* / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D006887:Hydroxycholecalciferols / Q000138:chemical synthesis*; D007408:Intestinal Absorption / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051381:Rats; D013056:Spectrophotometry, Ultraviolet
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D002118:Calcium