Synthesis of (25S)-[26-2H1]cholesterol and 1H N.m.r. signal assignments of the pro-R and pro-S methyl groups at C-25

Abstract

(25S)-[26-²H₁] Cholesterol (11) has been prepared from diosgenin (1), and the absolute configuration at C-25 of the crucial intermediate, (25R)-26-hydroxycholesterol (6), has been identified by X-ray crystallographic analysis. The two methyl groups at C-25 of cholesterol have been examined by ¹H n.m.r. spectroscopy and the two sets of doublet methyl signals due to 27-H and 26-H have been observed at δ_H 0.862 and 0.866 downfield from the internal reference. The former was assigned to 27-H, the pro-R methyl group attached at C-25, and the latter to 26-H, the pro-S methyl group attached at C-25. The ¹³C n.m.r. signal assignments of the methyl groups at C-25 reported by Popjak were confirmed on the basis of the signals of the deuteriated cholesterol (11).