Synthesis of [26,28-2H6]crinosterol, a synthetic intermediate of [26,28-2H6]brassinolide and [26,28-2H6]castasterone

Abstract

Stereoselective synthesis of [26,28-²H₆]crinosterol, [26,28-²H₆]-(22E,24S)-ergosta-5,22-dien-3β-ol(4), was achieved in ca. 50% overall yield from (20S)-20-formyl-6β-methoxy-3α,5-cyclo-5α-pregnane(5). Coupling of (5) with lithium acetylide gave a 2:1 mixture of separable products (6) and (7), whose configurations at C-22 were determined by chemical correlation with the known compounds (8) and (9), respectively. The triethylsilyl ether of the 22R isomer (6) was lithiated and then treated with [²H₃]iodomethane, to provide, after desilylation, the [²H₃]acetylenic alcohol (10). Partial hydrogenation of (10) with Lindlar catalyst followed by orthoester Claisen rearrangement yielded the [²H₃]ester (12), whose ester group was reduced to a trideuteriomethyl group. Acid treatment of the resulting [²H₆]ether (13) afforded [26,28-²H₆]crinosterol (4), the deuterium content of which was 98%.