Synthesis of Lanosterol Analogs with Lengthened Side Chains and Their Effects on Cholesterol Biosynthesis from Lanosterol

Abstract

Starting from 3β-acetoxy-25, 26, 27-trinorlanost-8-en-24-al (1), eight lanosterol analogs (10-17) with longer side chains side chains than that of lanosterol were synthesized by Wittig reaction followed by catalytic hydrogenation. Cholesterol biosynthesis was examined in rat hepatic subcellular preparation (S₁₀) incubated with [24-³H]-lanosterol in the presence of each of the eight lanosterol analogs. Some of the analogs (10 and 12) caused slight inhibition, but 16 and 17 showed no inhibitory effect. The structure-inhibitory activity relationship of lanosterol analogs on cholesterol biosynthesis from lanosterol is discussed.