Steroids. Part XXXV. Preparation of the epimeric 2-hydroxy-19-nor-5α-cholestanes

Abstract

2β,19-Epoxy-5α-cholestane, readily obtained from 5α-cholestan-2β-ol by treatment with lead tetra-acetate, on acetolysis with acetic anhydride catalysed by pyridinium hydrochloride or by boron trifluoride gave a variety of products, from which were derived 5α-cholestan-19-oic acids, 5α-cholest-1- and -2-en-19-aldehydes, and 5α-cholestan-19-ols. 2α-Acetoxy- and 2α-methoxy-5α-cholestan-19-oic acids resisted decarboxylation; the inseparable mixture of 5α-cholest-1- and-2-en-19-als when irradiated underwent decarbonylation to give 19-nor-5α-cholest-1-ene.

An improved preparation of 19-nor-5α-cholest-1-ene from 5α-cholest-1-ene was devised. Conversion of the latter into 1α-bromo-5α-cholestan-2β-ol followed by treatment with lead tetra-acetate gave 1α-bromo-2β,19-epoxy-5α-cholestane. This was converted with zinc–ethanol into 5α-cholest-1-en-19-ol, which was oxidised to 5α-cholest-1-en-19-al with Jones reagent. Irradiation of this aldehyde gave 19-nor-5α-cholest-1-ene, converted by hydroboration (bis-3-methyl-2-butylborane) into 19-nor-5α-cholestan-2α-ol (56%), 19-nor-5α-cholestan-2β-ol (28%), and the isomeric 19-nor-1α-ol (4%) and 19-nor-1β-ol (12%), which were separated by column chromatography, followed by preparative t.l.c.