Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland.
Carbohydr Res. 2013 Aug 9;377:4-13. doi: 10.1016/j.carres.2013.05.013. Epub 2013 May 28.
Geometry optimizations at the PM3 level were performed for diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside and its N-protonated form. Next, B3LYP/6-311++G(**) level geometry optimizations were carried out, albeit on a simpler model. The relative Gibbs free energies and geometry parameters are presented for the optimized structures. Conformational analysis concerning the clockwise (cw) and counterclockwise (ccw) arrangements of the OH groups as well as the three orientations of the NH2 and CH2OH groups was performed. Furthermore, a full scan of all the possible locations of the diosgenyl moiety in relation to the sugar ring in the target compounds was done. The PM3 optimization results indicate that diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside exists as a mixture of many rotamers. Of these, ccw conformers as well as the -ac orientation of the aglycone (ca -100° for torsion angle φ) are preferred. In the case of the N-protonated glucoside one rotamer is dominant in the mixture (population>60%). Only the cw arrangement is stable in the protonated form, because of steric and electronic repulsion between the charged ammonium group and the hydrogen atom of the neighbouring 3-OH group. The gauche-trans (gt) orientation of the CH2OH group is favourable to both neutral and protonated forms of diosgenyl glucosides at the PM3 level. DFT studies also predict conformational mixtures for both neutral and protonated forms of simplified diosgenyl 2-amino-2-deoxy-β-D-glucopyranosides. These investigations showed unequivocally the preference for the ccw arrangement over cw, and that values of angle φ concur with the exo-anomeric effect. The B3LYP functional predicts the greater stability of the gt and tg orientations for the neutral and protonated analogues respectively. According to both PM3 and B3LYP calculations, torsion angle ψ has only a minor influence on the conformational energy. The importance of the geometry parameters affecting the stability of these conformers appears to be as follows: angle φ≈NH2/ccw/cw>gg/gt/tg>angle ψ.
对薯蓣皂苷 2-氨基-2-去氧-β-D-吡喃葡萄糖苷及其质子化形式进行了 PM3 水平的几何优化。接下来，尽管采用了更简单的模型，但仍进行了 B3LYP/6-311++G(**)水平的几何优化。给出了优化结构的相对吉布斯自由能和几何参数。对 OH 基团的顺时针 (cw) 和逆时针 (ccw) 排列以及 NH2 和 CH2OH 基团的三个取向进行了构象分析。此外，对目标化合物中薯蓣皂苷部分相对于糖环的所有可能位置进行了全扫描。PM3 优化结果表明，薯蓣皂苷 2-氨基-2-去氧-β-D-吡喃葡萄糖苷以许多旋转异构体的混合物形式存在。其中，ccw 构象以及糖苷配基的 -ac 取向（扭转角 φ 约为-100°）是首选的。在质子化糖苷的情况下，混合物中只有一种旋转异构体占主导地位（丰度>60%）。由于带电荷的铵基团和相邻 3-OH 基团上的氢原子之间的空间位阻和电子排斥，只有 cw 排列在质子化形式中是稳定的。在 PM3 水平上，CH2OH 基团的 gauche-trans (gt) 取向对中性和质子化形式的薯蓣皂苷都有利。DFT 研究还预测简化的薯蓣皂苷 2-氨基-2-去氧-β-D-吡喃葡萄糖苷的中性和质子化形式的构象混合物。这些研究明确表明，ccw 排列优于 cw 排列，并且 φ 角的值与端基效应一致。B3LYP 函数预测中性和质子化类似物的 gt 和 tg 取向分别具有更大的稳定性。根据 PM3 和 B3LYP 计算，扭转角 ψ 对构象能的影响较小。影响这些构象稳定性的几何参数的重要性如下：φ 角≈NH2/ccw/cw>gg/gt/tg>ψ 角。
