El-Badri Mohamed H, Willenbring Dan, Tantillo Dean J, Gervay-Hague Jacquelyn
University of California, Davis, Department of Chemistry, One Shields Avenue, Davis, California 95616, USA.
J Org Chem. 2007 Jun 22;72(13):4663-72. doi: 10.1021/jo070229y. Epub 2007 Jun 1.
Stereoselective synthesis of beta-mannosides is one of the most challenging linkages to achieve in carbohydrate chemistry. Both the anomeric effect and the C2 axial substituent favor the formation of the axial glycoside (alpha-product). Herein, we describe mechanistic studies on the beta-selective glycosidation of trimethylene oxide (TMO) using mannosyl iodides. Density functional calculations (at the B3LYP/6-31+G(d,p):LANL2DZ level) suggest that formation of both alpha- and beta-mannosides involve loose S(N)2-like transition-state structures with significant oxacarbenium character, although the transition structure for formation of the alpha-mannoside is significantly looser. alpha-Deuterium kinetic isotope effects (alpha-DKIEs) based upon these computed transition state geometries match reasonably well with the experimentally measured values: 1.16 +/- 0.02 for the beta-linkage (computed to be 1.15) and 1.19 +/- 0.05, see table 2 for the alpha-analogue (computed to be 1.26). Since it was unclear if beta-selectivity resulted from a conformational constraint induced by the anomeric iodide, a 4,6-O-benzylidine acetal was used to lock the iodide into a chairlike conformation. Both experiments and calculations on this analogue suggest that it does not mirror the behavior of mannosyl iodides lacking bridging acetal protecting groups.
β-甘露糖苷的立体选择性合成是碳水化合物化学中最难实现的连接方式之一。端基异构效应和C2轴向取代基都有利于轴向糖苷（α-产物）的形成。在此，我们描述了使用碘代甘露糖对环氧丙烷（TMO）进行β-选择性糖苷化的机理研究。密度泛函计算（在B3LYP/6-31+G(d,p):LANL2DZ水平）表明，α-和β-甘露糖苷的形成都涉及具有显著氧碳鎓特征的类似SN2的松散过渡态结构，尽管α-甘露糖苷形成的过渡结构明显更松散。基于这些计算出的过渡态几何结构的α-氘动力学同位素效应（α-DKIEs）与实验测量值相当吻合：β-连接为1.16±0.02（计算值为1.15），α-类似物为1.19±0.05，α-类似物的计算值见表2（计算值为1.26）。由于不清楚β-选择性是否由端基碘化物诱导的构象限制导致，因此使用4,6-O-亚苄基缩醛将碘化物锁定为椅状构象。对该类似物的实验和计算均表明，它并不反映缺乏桥连缩醛保护基的碘代甘露糖的行为。
