Bohl M, Kaufmann G, Hübner M, Reck G, Kretschmer R G
J Steroid Biochem. 1985 Dec;23(6A):895-900. doi: 10.1016/0022-4731(85)90044-5.
The molecular structure and strain energy of 4-en-3-one steroids in two different A-ring conformations are calculated by means of a molecular mechanics technique. The computations for the isolated molecules provide the following order of increasing stability of the inverted A-ring conformers: 10-methyl, 19-nor, 9-ene compound. This tendency is in agreement with X-ray structure data for single crystals. The normal 1 alpha, 2 beta-half chair conformation of 10-methyl steroids is found to be stabilized by bond angles, mainly at C10, and non-bonded interactions from the 10-methyl group. Pitzer strains favour the inverted 1 beta, 2 alpha-half chair conformation in the case of 4,9-diene-3-one compounds. Binding affinities to the progesterone receptor decrease in the series: 19-nor, 9-ene, 10-methyl compound. In view of this ordering, the calculated relative stabilities of A-ring conformers are in conflict with a conformation-controlled receptor binding. Variations of receptor bond strengths are supposed to be more strongly influenced by a steric hindrance of the 10-methyl group and/or steroid-backbone flexibility.
采用分子力学技术计算了两种不同A环构象的4-烯-3-酮甾体的分子结构和应变能。对孤立分子的计算给出了反式A环构象异构体稳定性增加的如下顺序：10-甲基、19-降、9-烯化合物。这种趋势与单晶的X射线结构数据一致。发现10-甲基甾体的正常1α,2β-半椅式构象通过键角（主要在C10处）以及10-甲基的非键相互作用而得以稳定。在4,9-二烯-3-酮化合物的情况下，皮策应变有利于反式1β,2α-半椅式构象。与孕酮受体的结合亲和力按以下顺序降低：19-降、9-烯、10-甲基化合物。鉴于这种排序，计算得到的A环构象异构体的相对稳定性与构象控制的受体结合相矛盾。受体键强度的变化被认为更强烈地受到10-甲基的空间位阻和/或甾体主链柔性的影响。
