A Novel Facile Synthesis of Cholesta-5,7-Diene-3β,25-Diol, the Precursor of 25-Hydroxyvitamin D3

Abstract

An efficient four-step procedure is described for the synthesis of cholesta-5,7-diene-3β,25-diol from 7-dehydrodesmosterol in an overall yield of 72.4%. The 3-hydroxy group of 7-dehydrodesmosterol is protected as the acetate and the 5,7-diene system as a hetero Diels–Alder adduct with 4-phenyl-1,2,4-triazoline-3,5-dione. The key step in this synthesis is a very mild method for the hydroxybromination of the Diels–Alder adduct with N-bromosuccinimide in water, followed by reduction and deprotection with LiAlH4. This method gives cholesta-5,7-diene-3β,25-diol in a better yield than those reported previously and the reagents that are used are all relatively cheap, non-toxic and stable.