Laboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences , Leninsky Prospect 47, 119991 Moscow, Russia.
J Org Chem. 2017 Sep 1;82(17):8897-8908. doi: 10.1021/acs.joc.7b01167. Epub 2017 Aug 15.
The strength of 1,3-syn-diaxial repulsion was evaluated for main types of protecting groups (alkyl, silyl, and acyl) usually used in carbohydrate chemistry. As molecular probes for this study, derivatives of isopropyl 2-O-benzyl-4,6-O-benzylidene-α-d-idopyranoside bearing allyl, acetyl, and tert-butyldiphenylsilyl (TBDPS) protecting groups at O-3 were prepared from p-methoxyphenyl d-galactopyranoside. The equilibrium between S and C conformations in these compounds was investigated using J and J coupling constants that were determined from 1D H NMR and 2D J-resolved HMBC spectra in various solvents. The analysis of the corresponding coupling constants calculated using DFT/B3LYP/pcJ-1 approximation applied to conformations optimized at DFT/B3LYP/6-311++G** level supported the investigation. Proportions of conformers in the equilibrium revealed the highest repulsion between the 3-allyloxy group and the isopropoxy aglycon and its dependence on the solvent polarity. Differences in the conformational behavior of 3-O-allyl and 3-O-acetyl-α-d-idopyranoside derivatives complied with the notion that higher electron density on O-3 increased 1,3-syn-diaxial repulsion. 3-O-TBDPS derivative existed mainly in C conformation. The attenuation of the 1,3-syn-diaxial repulsive interaction indicates that TBDPS has stereoelectronic properties that may have significance in context of fixing unnatural pyranoside conformation with the help of silyl groups but have been disregarded until now.
评估了 1,3-顺二轴排斥力的强度，涉及在碳水化合物化学中常用的主要保护基（烷基、硅基和酰基）。作为这项研究的分子探针，从对甲氧基苯-d-半乳糖吡喃糖苷制备了在 O-3 位带有烯丙基、乙酰基和叔丁基二苯基硅基（TBDPS）保护基的异丙基 2-O-苄基-4,6-O-亚苄基-α-d-异吡喃糖苷的衍生物。使用从一维 1H NMR 和二维 J 分辨 HMBC 光谱在各种溶剂中确定的 J 和 J 偶合常数研究了这些化合物中 S 和 C 构象之间的平衡。使用 DFT/B3LYP/pcJ-1 逼近计算的相应偶合常数的分析应用于在 DFT/B3LYP/6-311++G**水平优化的构象，支持了这项研究。平衡中构象的比例揭示了 3-烯丙氧基与异丙烯基糖苷之间的最大排斥作用及其对溶剂极性的依赖性。3-O-烯丙基和 3-O-乙酰基-α-d-异吡喃糖苷衍生物的构象行为差异符合这样的观点，即 O-3 上的电子密度增加会增加 1,3-顺二轴排斥力。3-O-TBDPS 衍生物主要以 C 构象存在。1,3-顺二轴排斥相互作用的减弱表明，TBDPS 具有立体电子性质，这在借助硅基固定非天然吡喃糖苷构象方面可能具有重要意义，但直到现在一直被忽视。
