Sridharan R, Desai U R, Rao R M, Trivedi G K
Department of Chemistry, Indian Institute of Technology, Powai, Bombay.
Steroids. 1993 Apr;58(4):170-7. doi: 10.1016/0039-128x(93)90064-t.
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 chemical shift variation, and application of a modified Karplus equation. The steroids studied include 6 beta-bromocholest-4-en-3-one (3), 4,6 beta-dibromocholest-1,4-dien-3-one (2), 2 alpha,4,6 beta-tribromocholest-4-en-3-one (1), and (25R)-2 alpha,6 beta-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 2 alpha position is responsible for the inversion of the A ring to inverted 1 beta,2 alpha-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 2 alpha-bromosubstituted steroids. Complete assignment of the 13C and 1H resonances of two of the steroids studied (3 and 4) is presented.
通过协同应用高分辨率一维和二维核磁共振（NMR）技术，如同核和异核相关光谱、瞬态和稳态核Overhauser效应光谱、温度依赖性化学位移变化以及应用修正的Karplus方程，研究了四种不同功能化的溴代4-烯-3-酮甾体中A环和B环的构象偏好。所研究的甾体包括6β-溴胆甾-4-烯-3-酮（3）、4,6β-二溴胆甾-1,4-二烯-3-酮（2）、2α,4,6β-三溴胆甾-4-烯-3-酮（1）和（25R）-2α,6β-二溴螺甾-4-烯-3-酮（4）。甾体1-4通过适当的4-烯-3-酮甾体的酸催化或自由基溴化反应制备。该研究深入了解了这些溴代甾体A环和B环构象偏好的影响因素。2α位的溴取代导致A环反转成1β,2α-半椅式构象。4-溴与羰基氧之间的电子相互作用进一步扭曲了A环构象。A环的反转对B环椅式构象有伴随的扭曲作用。未发现A环和B环的构象偏好受侧链或含氧环系统的传递效应影响。温度依赖性NMR研究表明，2α-溴代甾体的A环构象灵活性降低。给出了所研究的两种甾体（3和4）的13C和1H共振的完全归属。
