Synthesis and properties of 4,6-propanosteroids

A method has been developed for the synthesis of 4Β,6-propanocholestanes whereby a three-carbon synthon is added to cholest-4-en-6-one using the lithiated organocopper reagent of acetone N,N-dimethylhydrazone. Hydrolysis of 4Β-(2'-oxopropanyl)-5α-cholestan-6-one 2'-dimethylhydrazone, followed by an intramolecular Aldol condensation afforded 4α,5α- dihydrobenzo[4,5,6]cholest-4-en-5'(6'H)-one. Reduction of the double bond using a variety of methods gave only 4α,4',5α,6α-tetrahydrobenzo[4,5,6]cholest-4-en-5'(6'H)-one which was converted into the corresponding parent hydrocarbon, having 6α(H)-configuration. Access to the isomeric 6Β(H)-series was obtained through boron trifluoride rearrangement of 4'α,6-epoxy-4α,4',5α,5',6α,6'-hexahydrobenzo[4,5,6]cholest-4-one to 4α,5α,5',6'-tetrahydrobenzo[4,5,6]=cholest-4-en-4'(6ΒH)-one, followed by a Wolff-Kishner reduction of the 4'-carbonyl group. The Carroll variation of the Claisen rearrangement was investigated as a route to the 4α,6-propanocholestanes. The structural and conformational properties of the compounds synthesised in this investigation were studied using 1H n.m.r. and 13C n.m.r. spectrometry, and circular dichroism