STEREOSPECIFIC ASSOCIATION OF C-20 EPIMERS OF -HYDROXY-16-OXO-24-NOR-17-AZACHOL-5-ENO-23-NITRYLE

The cryoscopic measurements show that title compounds are strongly ass ociated in CHCl3 solutions. The association of the 20R epimer is disti nctly less pronounced than that of the 20S epipmer. Self-association o f the 20S epimer leads to the formation of very large complexes, The 2 0R epimer forms associates via water molecules. The dissimilarity may be explained in terms of different accessibility of the lactam carbony l groups in the two epimers for the association. It is proposed that t he association process is controlled by the configuration at the carbo n atom C(20) and conformation around the C(20)-C(22) bond. Populations of side chain conformations of both epimers were determined by means of proton nuclear magnetic resonance. It was found for the 20R epimer that the t and the -g rotamers are almost equally populated, and the r otamer +g is excluded. For the 20 S epimer the +g rotamer predominates over the t one, and the -g rotamer is excluded. The NMR data are full y consistent with the results of the molecular modelling studies.