Stereoselective synthesis of the C-24 and C-25 stereoisomeric pairs of 24-ethyl-26-hydroxy- and 24-ethyl-[26-2H]sterols and their Δ22-derivatives: reassignment of 13C n.m.r. signals of the pro-R and the pro-S methyl groups at C-25 of 24-ethylsterols

Abstract

Two C-24 and C-25 epimeric pairs of 24-ethyl-26-acid sterol derivatives (22)–(25) were stereoselectively synthesized via an ester-enolate Claisen rearrangement of the (22R)-(20) and (21) and (22S)-23E-ene derivatives (18) and (19). The absolute configuration at C-24 and C-25 of methyl (22E,24S,25S)-6β-methoxy-3α,5-cyclo-5α-stigmast-22-en-26-oate (22a) and (22E,24R,25R)-6β-methoxy-3α,5-cyclo-5α-stigmast-22-en-26-oic acid (24) were confirmed by X-ray crystallography. Four C-24 and C-25 epimeric pairs of 24-ethyl-[26-²H]-(34)–(37) and 24-ethyl-26-hydroxy-sterols (42)–(45) and their Δ²²-derivatives (38)–(41) and (46)–(49) have been synthesized in order to study the stereochemistry in the biosynthesis of (24R)- and (24S)-24-ethylsterol side-chains. The data showed that C-26 and C-27 arise biosynthetically from C-6 and C-2 of MVA, respectively.