Steroids. Part XXXIII. Attempted preparation of 19-nor-5α-cholestanes via 2β-hydroxy-5α-cholestan-19-oic acid

Abstract

5α-Cholestan-2β-ol (I) and lead tetra-acetate–iodine with irradiation gave the 2β,19-epoxide (II)(10%) and the 2β,19-hemiacetal (III)(50%), which was oxidised to the 19 → 2β-lactone (IV). This, on hydrolysis gave the 2β-hydroxy-acid (VIa), whose methyl ester by oxidation afforded the 2-keto-ester (VIIb), which was hydrolysed to an equilibrium mixture of the 2-keto-acid and the lactol [(VIIa)⇌(IXa)], from which the 2-keto-acid chloride (VIIc) could not be obtained, the product being the chloro-lactone (IXc). Reduction with sodium borohydride of the 2-keto-ester (VIIb) gave the 2α-hydroxy-ester (X)(75%) and the 2β-hydroxy-ester (VIb). Attempted decarboxylation of the 2β-methoxy-acid (VIc) and of the equilibrium mixture (VIIa)⇌(IXa) was unsuccesful. Dehydration of the 2β-hydroxy-ester (VIb), or treatment of its toluene-p-sulphonate with refluxing s-colidine, gave a mixture of the Δ¹- and Δ²-19-methyl esters represented by (XI), which resisted alkaline hydrolysis, but on reduction with lithium aluminium hydride gave a mixture of the Δ¹- and Δ²-19-ols represented by (XII), which could be oxidised to a mixture of the related aldehydes. Structures assigned are supported by u.v., i.r., and n.m.r. spectroscopy.