Bohl M, Schubert G, Ponsold K, Reck G, Höhne E, Simon K
Academy of Sciences, Central Institute of Microbiology and Experimental Therapy, Jena, DDR.
J Mol Graph. 1989 Sep;7(3):122-9, 153. doi: 10.1016/0263-7855(89)80015-3.
The influence of 11 beta-phenyl substitution upon 4,9-dien-3-one steroid-backbone conformations is calculated by means of the MM2p molecular mechanics scheme. In the case of steroids having a 13 beta configuration, the lowest strain energy is always evaluated for the conformational combination of rings A(inverted) B(normal) while, moreover, the 11 beta substitution increases the relative stability of the conformation A(normal) B(normal) compared to the nonsubstituted compound. Introduction of the 11 beta substituent causes some bowing of the energy-minimum structures in the A-ring region toward the beta side. For 13 alpha configurated steroids, the ring conformations A(inverted) B(normal) C(boat) and A(normal) B(inverted) C(twist/boat) are found to be energetically preferred. Quantitative description of different ring conformations using asymmetry and pseudorotational parameters as well as the comparison of molecular mechanics and available X-ray structure data give an impression of the conformational mobility. Whereas the effect of 11 beta substitution within a given ring conformation is limited, contributions to molecular flexibility can be found in the ability to adopt different basic conformations and in the occupation of near-minimum structures. An X-ray crystal structure analysis of a potential antiprogestational steroid has been performed, and the results are in good agreement with the calculated structure.
采用MM2p分子力学方法计算了11β-苯基取代对4,9-二烯-3-酮甾体骨架构象的影响。对于具有13β构型的甾体，总是对环A（反式）B（正常）的构象组合评估出最低的应变能，此外，与未取代的化合物相比，11β取代增加了构象A（正常）B（正常）的相对稳定性。11β取代基的引入导致A环区域中能量最低结构向β侧出现一些弯曲。对于13α构型的甾体，发现环构象A（反式）B（正常）C（船式）和A（正常）B（反式）C（扭曲/船式）在能量上更有利。使用不对称和假旋转参数对不同环构象进行定量描述，以及对分子力学和现有X射线结构数据进行比较，给出了构象流动性的印象。虽然在给定的环构象内11β取代的影响是有限的，但在采用不同基本构象的能力以及占据近最低能量结构方面可以发现对分子柔性的贡献。已对一种潜在的抗孕激素甾体进行了X射线晶体结构分析，结果与计算结构吻合良好。
