Tanaka Yoko

Synthesis and biological activity of 25,26,27-trisnor-vitamin D3 24-oic acid and its 1α-hydroxyl analog

Abstract Because 1,25-dihydroxy vitamin D undergoes side-chain cleavage and oxidation in vivo , an anticipated metabolite is 1α-hydroxy-trisnor-vitamin D 3 24-oic acid. A synthesis for this metabolite and trisnor-vitamin D 3 24-oic acid has been devised. Baeyer-Villiger rearrangement of 5,6-dibromo-24-oxo-cholesteryl acetate and its 1α-acetoxyl analog gave the corresponding cholenoate derivatives, and those were converted to trisnor-vitamin D 3 24-oic acid and its 1α-hydroxyl analog, respectively. The 1α-hydroxy-25,26,27-trisnor-vitamin D 3 24-oic acid (1α-OH-24-COOH trisnor-vitamin D 3 ) was tested for biological activity using rats fed a low calcium, vitamin D-deficient diet. It stimulated intestinal calcium transport 6 h after intravenous administration although the response is significantly less than that to an identical base of 1,25-dihydroxy vitamin D 3 (1,25-(OH) 2 D 3 ). This compound given at 125 ng per rat did not stimulate bone calcium mobilization.