Conformational analysis of A and B rings in 2-, 4-, and 6-bromosubstituted steroidal 4-en-3-ones by nuclear magnetic resonance

Article abstract of DOI:10.1016/0039-128X(93)90064-T

The conformational preference of A and B rings in four differently functionalized bromosubstituted 4-en-3-ones 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 6β-bromocholest-4-en-3-one (3), 4,6β-dibromocholest-1,4-dien-3-one (2), 2α,4,6β-tribromocholest-4-en-3-one (1), and (25R)-2α,6β-dibromospirost-4-en-3-one.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 bromosubsituted steroids.Bromosubstitution at the 2α position is responsible for the inversion of the A ring to inverted 1β,2α-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 distorsion 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 2α-bromosubstituted steroids.Complete assignment of the 13C and 1H resonances of two of the steroids studied (3 and 4) is presented.Keywords: 4-en-3-one steroids; two-dimensional nuclear magnetic resonance; bromosteroids; conformational analysis; total assignment; A and B rings