Yukuo Eguchi

Synthesis and biological activity of 1α-hydroxyvitamin D3

Abstract Hydroboration of cholesta-1,5-diene-3β-ol followed by alkaline-peroxide oxidation resulted in the formation of 1α- and 2α-hydroxy derivatives of cholesterol in nearly equal amounts. 1α-Hydroxycholesterol was then transformed to 1α-hydroxyvitamin D 3 , via 1α-hydroxycholest-5,7-diene-3β-ol. 1α-Hydroxyvitamin D 3 was as active as 25-hydroxyvitamin D 3 in the stimulation of intestinal calcium transport and bone mineral mobilization in intact rats, and moreover was able to produce both response in anephric rats similar to 1α,25-dihydroxyvitamin D 3 , the active metabolite of vitamin D 3 , as reported originally by DeLucas group.

A new synthetic method of 1α-hydroxy-7-dehydrocholesterol

Abstract Cholesta - 1,4,6 - trien - 3 - one ( 1 ) was converted to 3β - hydroxycholesta - 1,5,7 - triene ( 3 ) via the deconjugation procedure using t-BuOK in DMSO followed by the subsequent reduction with Ca(BH 4 ) 2 . The compound ( 3 ) readily reacted with 4-phenyl-1,2,4-triazoline-3,5-dione to yield the corresponding 1,4-addition product ( 4 ). Epoxidation of 4 with m -chloroperbenzoic acid resulted in the formation of the 1α,2α-epoxide ( 5 ) and the 1β,2β-epoxide ( 6 ) in the ratio 2:3. Reduction of 5 with LAH under reflux in THF afforded the titled compound ( 7 ). The same reduction of 6 gave 2β-hydroxy- and 1β - hydroxy - 7 - dehydrocholesterol ( 8 and 9 ) in the ratio 8:1. The compound ( 4 ) can be obtained in 25% yield from 1 without any purification of the intermediate compounds; cholesta - 1,5,7 - trien - 3 - one ( 2 , a very unstable compound) and 3 . Since 1 is obtained readily from cholesterol in high yield, the present study provides a simple and efficient synthetic method of 1α-hydroxycholecalciferol and is reasonably expected to be applicable in the synthesis of 12,25-dihydroxycholecalciferol and the other metabolites of vitamin D 3 .