CONFORMATIONAL-ANALYSIS OF A-RINGS AND B-RINGS IN 2-BROMOSUBSTITUTED, 4-BROMOSUBSTITUTED, AND 6-BROMOSUBSTITUTED STEROIDAL 4-EN-3-ONES BY NUCLEAR-MAGNETIC-RESONANCE

The conformational preference of A and B rings in four differently functionalized bromosubstituted 4-en-3-one steroids is studied by concerted application of high-resolution one- and two-dimensional nuclear magnetic resonance (NMR) techniques, such as homonuclear and heteronuclear correlated spectroscopy, transient and steady-state nOe spectroscopy, temperature-dependent chemical shift variation, and application of a modified Karplus equation. The steroids studied include 6beta-bromocholest-4-en-3-one (3), 4,6beta-dibromocholest-1,4-dien-3-one (2), 2alpha,4,6beta-tribromocholest4-en-3-one (1), and (25R)-2alpha,6beta-dibromospirost-4-en-3-one (4). Steroids 1-4 were prepared by either acid-catalyzed or free-radical bromination from appropriate 4-en-3-one steroid. The study has yielded an insight into the factors responsible for conformational preferences of the A and B rings of these bromosubstituted steroids. Bromosubstitution at the 2a position is responsible for the inversion of the A ring to inverted 1beta,2alpha-halfchair conformation. The electronic interaction between 4-bromine and carbonyl oxygen distorts the A-ring conformation further. Inversion of the A ring has a concomitant effect of distortion in the chair form of the B ring. Conformational preferences of A and B rings are not found to be influenced by transmission effect of a side chain or oxygenated ring system.Temperature-dependent NMR studies indicate the reduced conformational flexibility of the A ring for 2alpha-bromosubstituted steroids. Complete assignment of the C-13 and H-1 resonances of two of the steroids studied (3 and 4) is presented.