Synthesis and biological activity of 25,26-dihydroxycholecalciferol

25,26-Dihydroxycholecalciferol (25,26-dihydroxyvitamin D₃), a metabolite of vitamin D3 preferentially active on intestine has been synthesized. This compound was prepared by converting 3β-hydroxy-27-norcholest-5-en-25-one to 25,26-epoxy-5-cholesten-3β-o1 and base-catalyzed hydrolysis of the latter to 5-cholestene-3β,25,26-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 μg, the compound stimulates intestinal calcium transport, but has no effect on bone calcium mobilization in rats maintained on a vitamin D-deficient, low calcium didt. Higher doses (2.5 μg) 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.