Synthesis of (25R)-[26-2H1]cholesterol and 1H n.m.r. and h.p.l.c. resolution of (25R)- and (25S)-26-hydroxycholesterol

Abstract

Yamogenin acetate (1) was isolated from crude diosgenin acetate and converted into (25S)-26-hydroxycholesterol (6a). The absolute configuration at C-25 of (6a) was determined by X-ray crystallography. (25R)-[26-²H₁] Cholesterol (10) was prepared by reduction of the 26-tosyloxy group by LiAl²H₄. Reverse-phase h.p.l.c. resolution without derivatiration was developed for the diastereoisomers, (25R)- and (25S)-26-hydroxycholesterol. The (+)- or (–)-MTPA esters of these diastereoisomers showed distinctive ¹H n.m.r. signals for 26-H.