Syntheses of C20 13α-Steroidal Progestagens

In order to examine the physiological activity the preparation of 3, 17-dihydroxy-19-nor-13α-pregna-1, 3, 5 (10)-trien-20-one 17-acetates (IIId, IXc) has been undertaken. The Grignard reaction of 13α-estrone (I) with ethynylmagnesium bromide provided two epimeric 17-ethynyl-17-ols (II, VIIIa), which on hydration were led to 3, 17-dihydroxy-19-nor-13α-pregnatrien-20-ones (IIIa, IXa). Elucidation of the stereochemistry at C-17 was attained by the degradative means. First, IIIa was submitted to metal hydride reduction, usual acetylation followed by Serini reaction to afford 19-nor-13α-pregnatrien-20-one (V). Upon treatment with base V was readily transformed into the thermody-namically much more stable 17α-epimer (VIb), whose structure was confirmed by leading to the known 13α-estratriene-3, 17α-diol (VIIa) employing Baeyer-Villiger reaction. The desired compounds were unequivocally obtained from the 3, 17-diacetates (IIIc, IXb) by partial hydrolysis, respectively.