A NEW SYNTHESIS OF CHOLESTEROL AND RELATED C27 STEROIDS

A new method has been developedfor the construction of the side chain of C27 sterols from C21-20-keto steroids and used for the synthesis of Δ16- and cis-Δ17(20)-cholesterol. The α,β-unsaturated nitrile 1, obtained by the dehydration of the cyanohydrin of pregnenolone acetate, was treated with isoamylmagnesium bromide to give the α,β-unsaturated ketone 3, which was isomerized to the β,γ-unsaturated ketone 6 by treatment with base. The 22-keto group of 3 and 6 was then converted into the 22-methlene group by treatment of their 22-ethylene thioketal derivatives with lithium and ethylamine to give cis-Δ17(20)- and Δ16-cholesterol, respectively. Alternatively, the enone 3 was converted into an allyl ether 22, which was then treated with lithium and ethylamine to give cis-Δ17(20)-cholesterol. The 17-20 double bond of 3 and the 16-17 double bond of 6 has been selectively reduced to give 22-ketocholesterol, which was then converted into cholesterol via its 22-ethylene thioketal. © 1969, American Chemical Society. All rights reserved.