A Concise Synthesis of 25-Hydroxycholesterol from Hyodesoxycholic Acid

A simple, efficient and economical method has been developed for the synthesis of 25-hydroxycholesterol in seven steps from hyodesoxycholic acid with an overall yield of 39%. The preparation of the 3β-tetrahydropyranyloxychol-5-en-24-al from 3β-tetrahydropyranyloxychol-5-en-24-oic acid methyl ester with di-isobutylaluminium hydride was achieved instead of using the conventional two-step reaction, thus avoiding the use of the toxic oxidant CrO 3 . The terminal product was obtained by hydroxybromination of desmosterol with N-bromosuccinimide/H 2 0, followed by reduction and deprotection of the halohydrins with LiAlH 4 . This simplified route gave an increased overall yield and used economical and environmentally benign reagents.