The Influence of the Electron Density in Acyl Protecting Groups on the Selectivity of Galactose Formation.
The Influence of the Electron Density in Acyl Protecting Groups on the Selectivity of Galactose Formation.
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DOI：
10.1021/jacs.2c05859
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发表时间：
2022-11-09
影响因子：
15
通讯作者：
Pagel, Kevin
中科院分区：
文献类型：
--
作者：
Greis, Kim;Leichnitz, Sabrina;Kirschbaum, Carla;Chang, Chun-Wei;Lin, Mei-Huei;Meijer, Gerard;von Helden, Gert;Seeberger, Peter H.;Pagel, Kevin
1，2-顺式糖苷键的立体选择性形成是碳水化合物合成中的主要瓶颈。在这里，我们研究如何在酰基保护基团的电子密度影响的立体选择性，通过微调远程参与的效率。富电子C4-新戊酰化半乳糖结构单元显示出前所未有的α-选择性。另一方面，具有吸电子基团的三氟乙酰化对应物表现出较低的选择性。氦纳米液滴中的低温红外光谱和密度泛函理论计算揭示了该反应的二氧杂环戊烯型中间体的存在，这表明特戊酰基保护基团的远程参与是特戊酰基化结构单元的高α-选择性的起源。根据这些发现，基于合理的考虑开发了用于糖合成的α-选择性半乳糖结构单元，并随后用于显示完全立体选择性的自动化聚糖组装。基于糖基化反应的选择性和红外光谱和密度泛函理论的结果，我们提出了一种机制，这些反应可以进行。
The stereoselective formation of 1,2-cis-glycosidic bonds is a major bottleneck in the synthesis of carbohydrates. We here investigate how the electron density in acyl protecting groups influences the stereoselectivity by fine-tuning the efficiency of remote participation. Electron-rich C4-pivaloylated galactose building blocks show an unprecedented α-selectivity. The trifluoroacetylated counterpart with electron-withdrawing groups, on the other hand, exhibits a lower selectivity. Cryogenic infrared spectroscopy in helium nanodroplets and density functional theory calculations revealed the existence of dioxolenium-type intermediates for this reaction, which suggests that remote participation of the pivaloyl protecting group is the origin of the high α-selectivity of the pivaloylated building blocks. According to these findings, an α-selective galactose building block for glycosynthesis is developed based on rational considerations and is subsequently employed in automated glycan assembly exhibiting complete stereoselectivity. Based on the obtained selectivities in the glycosylation reactions and the results from infrared spectroscopy and density functional theory, we suggest a mechanism by which these reactions could proceed.
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影响因子：
62.1
作者：
Adero PO;Amarasekara H;Wen P;Bohé L;Crich D
通讯作者：
Crich D
影响因子：
5.2
作者：
Greis, Kim;Kirschbaum, Carla;Pagel, Kevin
通讯作者：
Pagel, Kevin
影响因子：
3.1
作者：
Bohe, Luis;Crich, David
通讯作者：
Crich, David
DOI：
10.1002/anie.201510983
发表时间：
2016-03-01
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
González Flórez AI;Mucha E;Ahn DS;Gewinner S;Schöllkopf W;Pagel K;von Helden G
通讯作者：
von Helden G
影响因子：
16.6
作者：
Elferink, Hidde;Mensink, Rens A.;Boltje, Thomas J.
通讯作者：
Boltje, Thomas J.