Synthesis of [26,27-2H6] cholesterol and derivatives substituted in the side chain

Abstract

The carbanion derived from 24-phenylsulphonylchol-5-en-3β-ol 3-tetrahydropyranyl ether (6) reacted with [²H₆]acetone to give the 24-phenylsulphonyl-25-hydroxy[26,27-²H₆]cholesterol derivative (7a), which was reduced by sodium amalgam to a separable mixture of the labelled 25-hydroxycholesterol and cholest-5,24-dien-3β-ol (desmosterol) derivatives. [26,27-²H₆]Cholesterol has been obtained via a selective reduction of the Δ²⁴-unsaturation in [26,27-²H₆]desmosteryl benzoate with di-imide, or more efficiently by reducing 25-hydroxy[26,27-²H₆]cholesteryl 3,25-diacetate with lithium in ethylamine, without significant loss of label. The labelled 24,25-dihydroxycholesterols were also prepared from [26,27-²H₆]desmosteryl benzoate.