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

Article abstract of DOI:10.1016/S0040-4020(01)97432-0

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(BH₄)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 D₃.