Alternative syntheses of 3-hydroxy-17-bromo-16,17-secoestra-1,3,5(10)-triene-16-nitrile and crystallographic studies of two intermediates

Abstract: Starting from estrone 3-benzyloxy-17-hydroxy-16,17-secoestra-1,3,5(10)-triene- 16-nitrile (1) was synthesized in several synthetic steps. This compound was the key intermediate in the syntheses of other 17-substituted-16,17-secoestrone derivatives. Among them 3-hydroxy-17-bromo-16,17-secoestra-1,3,5(10)-triene-16-nitrile (5) is of special interest, because of its antiestrogenic activity, with no estrogenic properties. For this reason an alternative pathway for the synthesis of this compound was sought. The structures of 3-benzyloxy-17-bromo-16,17-secoestra-1,3,5(10)-triene- 16-nitrile (compound 2) and 3-hydroxy-17-p-toluenesulphonyloxy-16,17-secoestra 1,3,5(10)-triene-16-nitrile (compound 4), intermediates in the two different synthetic pathways used to obtain the desired compound 5, were unambiguously proved by appropriate X-ray structural analyses. The puckering, asymmetry parameters and torsion angles of compounds 2 and 4 are discussed and molecular-mechanic calculations for them were performed.