Influence of side chain conformation and configuration on glycosyl donor reactivity and selectivity as illustrated by sialic acid donors epimeric at the 7-position.
Influence of side chain conformation and configuration on glycosyl donor reactivity and selectivity as illustrated by sialic acid donors epimeric at the 7-position.
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DOI：
10.1021/ja410683y
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发表时间：
2013-12-18
影响因子：
15
通讯作者：
Crich D
中科院分区：
文献类型：
--
作者：
Kancharla PK;Crich D
合成了两个7位N-乙酰基-40，5 N-恶唑烷保护的唾液酸硫苷差向异构体，并比较了它们在糖基化反应中的反应活性和立体选择性。研究表明，天然的7S-供体比非天然的7 R-异构体更具反应性和α-选择性。反应性的差异是由于侧链构象，特别是接近O 7的异头中心。在天然的7S-异构体中，O 7比在其非天然的7 R-差向异构体中更接近异头中心，因此能够更好地支持反应位点处的初始正电荷。选择性的差异也归因于侧构象，在非天然7 R系列中，侧构象垂直于供体的α面上方，因此比7S系列更大程度地屏蔽了供体。这些观察结果与早期的结论一致的侧链构象的反应性和选择性的影响来自构象锁定模型中的葡萄糖和半乳糖系列，并证实了这些影响主要是立体电子，而不是扭转的建议。侧链构象作为远程保护基团的糖基化立体选择性的影响因素和作为糖苷键形成和水解的酶促过程中的控制元素的可能相关性进行了讨论。综述了唾液酸糖苷异头构型的归属方法。
Two N-acetyl 4O,5N-oxazolidine-protected sialyl thioglycosides epimeric at the 7-position have been synthesized and their reactivity and stereoselectivity in glycosylation reactions compared. It is demonstrated that the natural 7S-donor is both more reactive and more α-selective than the unnatural 7R-isomer. The difference in reactivity is attributed to the side chain conformation and specifically to the proximity of O7 to the anomeric center. In the natural 7S-isomer O7 is closer to the anomeric center than in its unnatural 7R-epimer and therefore better able to support incipient positive charge at the locus of reaction. The difference in selectivity is also attributed to the side conformation, which in the unnatural 7R-series is placed perpendicularly above the α-face of the donor and so shields it to a greater extent than in the 7S-series. These observations are consistent with earlier conclusions on the influence of the side chain conformation on reactivity and selectivity derived from conformationally locked models in the glucose and galactose series and corroborate the suggestion that those effects are predominantly stereoelectronic rather than torsional. The possible relevance of side chain conformation as a factor in the influence of glycosylation stereoselectivity by remote protecting groups and as a control element in enzymic processes for glycosidic bond formation and hydrolysis are discussed. Methods for assignment of the anomeric configuration in the sialic acid glycosides are critically surveyed.
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影响因子：
15
作者：
Chuang, Hong-Yang;Ren, Chien-Tai;Wong, Chi-Huey
通讯作者：
Wong, Chi-Huey
影响因子：
15
作者：
CZARNIECKI, MF;THORNTON, ER
通讯作者：
THORNTON, ER
影响因子：
1.8
作者：
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通讯作者：
De Meo, Cristina
影响因子：
3.6
作者：
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通讯作者：
Sun, SX
影响因子：
3.6
作者：
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通讯作者：
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