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 fun ctionalized bromosubstituted 4-en-3-one steroids is studied by concert ed application of high-resolution one- and two-dimensional nuclear mag netic resonance (NMR) techniques, such as homonuclear and heteronuclea r 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-bromoch olest-4-en-3-one (3), 4,6beta-dibromocholest-1,4-dien-3-one (2), 2alph a,4,6beta-tribromocholest4-en-3-one (1), and (25R)-2alpha,6beta-dibrom ospirost-4-en-3-one (4). Steroids 1-4 were prepared by either acid-cat alyzed or free-radical bromination from appropriate 4-en-3-one steroid . The study has yielded an insight into the factors responsible for co nformational preferences of the A and B rings of these bromosubstitute d steroids. Bromosubstitution at the 2a position is responsible for th e inversion of the A ring to inverted 1beta,2alpha-halfchair conformat ion. 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. Co nformational preferences of A and B rings are not found to be influenc ed by transmission effect of a side chain or oxygenated ring system.Te mperature-dependent NMR studies indicate the reduced conformational fl exibility of the A ring for 2alpha-bromosubstituted steroids. Complete assignment of the C-13 and H-1 resonances of two of the steroids stud ied (3 and 4) is presented.