Can the stereochemical outcome of glycosylation reactions be controlled by the conformational preferences of the glycosyl donor?
Can the stereochemical outcome of glycosylation reactions be controlled by the conformational preferences of the glycosyl donor?
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DOI：
10.1016/s0008-6215(02)00043-5
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发表时间：
2002-04-17
影响因子：
3.1
通讯作者：
Whitfield, DM
中科院分区：
文献类型：
--
作者：
Nukada, T;Bérces, A;Whitfield, DM
先前对2，6-二-O-乙酰基-3，4-O-异亚丙基-D-吡喃半乳糖基阳离子及其甲醇加合物的静态和动态密度泛函理论研究导致了一种假设，即这些阳离子存在于两个构象族中，分别表征为S-2（O）和B-2，B-5。这些家族的不同之处在于环反转，每一个都有自己的反应性。对2，6-二-O-乙酰基-3，4-二-O-甲基-D-吡喃半乳糖基阳离子的新计算证实了这些趋势。去除异亚丙基基团允许更大的灵活性，但可以辨别两个构象家族，其中单环氧代碳正离子处于E-3构象，双环二氧杂环戊烯离子处于H-4（5）构象。这些单环阳离子的P-面上的攻击受到氢键和异头效应的支持。实验观察到的具有4，6-O-亚苄基保护基团的吡喃甘露糖基供体的高β-立体选择性和吡喃葡萄糖基供体的高α-立体选择性可以合理化，假设反式稠合的1，3-二氧六环仅允许一个构象异构体家族的群体。吡喃糖环的氢键和构象变化的组合响应于C-5-O-5-C-1-C-2扭转角的变化被确定为立体选择性的关键因素。基于这些观察，提出了一种设计主要存在于一个构象异构体家族中的面歧视糖基供体的策略。(C)2002年由Elsevier Science Ltd.出版
Previous static and dynamical density functional theory studies of the 2,6-di-O-acetyl-3,4-O-isopropylidene-D-galactopyranosyl cations and their methanol adducts has led to an hypothesis that these cations exist in two families of conformers characterized as S-2(O) and B-2,B-5, respectively. These families differ by ring inversion, each with its own reactivity. New calculations on the 2,6-di-O-acetyl-3,4-di-O-methyl-D-galactopyranosyl cation confirmed these trends. Removing the isopropylidene group allows more flexibility, but two families of conformers can be discerned with the monocyclic oxocarbenium ions in the E-3 conformation and the bicyclic dioxolenium ions in the H-4(5) conformation. Attack on the P-face of these monocyclic cations is favored by hydrogen bonding and the anomeric effect. The experimentally observed high beta-stereoselectivity of mannopyranosyl donors and high alpha-stereoselectivity of glucopyranosyl donors with the 4,6-O-benzylidene protecting groups can be rationalized assuming that the trans-fused 1,3-dioxane ring allows population of only one family of conformers. The combination of hydrogen bonding and conformational changes of the pyranose ring in response to the C-5-O-5-C-1-C-2 torsion angle changes are identified as key factors in stereo selectivity. Based on these observations a strategy to design face discriminated glycosyl donors that exist predominantly in only one family of conformers is proposed. (C) 2002 Published by Elsevier Science Ltd.