CONSTRUCTION OF THE SIDE-CHAIN IN 14-BETA-ANDROST-5-ENE DERIVATIVES -PREPARATION OF 14-BETA-PREGNENOLONE

Stepwise side-chain construction schemes leading to pregnane derivativ es were tested in the 14 beta-androst-5-ene series. 6 beta-Methoxy-3 a lpha,5-cyclo-5 alpha,14 beta-androstan-17-one (I) gave after methylena tion and hydroboration the 17 alpha-hydroxymethyl derivative III. Subs equent oxidation to the aldehyde VI, Grignard reaction with methylmagn esium iodide, and reoxidation led to the ketone VII and to the isomeri c 17 beta-derivative VIII as a minor product. Final i-steroid cleavage of VII furnished the known 14 beta,17 alpha-pregnenolone IX; the mino r product VIII gave the 17 beta-isomer X. Alternatively, the ketone X was prepared from 6 beta-methoxy-3 alpha,5-cyclo-5 alpha,14 beta-andro stan-17 alpha-ol p-toluenesulfonate (XI) by cyanide substitution, diis obutylaluminum hydride reduction to the aldehyde XIV, and further as d escribed for IX. The mass and NMR spectra of the four pregnenolone der ivatives IX, X, XVIII, and XIX, isomeric in positions 14 and 17, were studied.