PartiaI Syntheses of 21,27 -Bisnordemissidine from Epiandrosterone and Dehydroepiandrosterone Acetates. Crystal and Molecular Structure of 21,27 -Bisnordemissidine Hydrobromide

Sa？etak Stereoselective syntheses of 21,27-bisnordemissidine from epiandrosterone acetate (1) and dehydroepiandrosterone acetate (la) are described in this work. These syntheses involve in sequence: a) stereospecific addition of ？-picolyl-Iithium to the C-17 carbonyl group of 1 (la); b) regio- and chemoselective 17,20-dehydration of the formed diol 2 (2a) leading to 3~-acetoxy-17-picolinylidene- -5a-androstane (3) or the corresponding derivative 3a; c) regiospecific allylic oxidation of C-16 in 3 (3a) by Se02 to 4 and chromic acid oxidation to the crucial intermediates (5a-5d); d) stereospecific intramolecular reductive cyclization reaction of 5a-5d, under carefully chosen reaction conditions, leading to 3~-acetoxy- -21,27-bisnor-5a-solanidane (6); e) hydrolysis of 6 with conc. aq. HBr to the target molecule of 21,27-bisnordemissidine hydrobromide (7); and f) alkaline treatment of 6 and 7 with KOH in MeOH affording 21,27-bisnordemissidine (11). The structure of 7 has been unambiguously proved by the appropriate X-ray structural analysis. Detection and isolation of some intermediates and by-products (8, 9 and 10) during catalytic hydrogenation of 5c and 5d pointed to a possible mechanism of the last and crucial step of the synthesis of 21,27-bisnordemissidine