荷兰奈梅亨·拉德堡德大学Thomas J. Boltje团队报道了甘露醛酸糖基供体中C-3酰基邻基参与的机制。相关研究成果于2024年12月18日发表于国际一流学术期刊《美国化学会杂志》。

寡糖合成的主要挑战之一是糖苷键的立体选择性引入。为了理解和控制糖基化反应，需要进行彻底的机理研究。核磁共振波谱发现的反应中间体通常无法解释糖基化的立体化学结果。因此，根据科廷-哈米特方案，反应可能通过难以检测的低丰度反应中间体进行。研究人员之前观察到甘露型糖可以参与C-3酰基邻近基团的参与。

该文中，研究人员报告了检测由甘露糖醛酸供体中C-3邻近基团参与引起的糖基二恶阴离子。使用一套交换核磁共振技术，能够剖析C-3酰基参与之前的构象环翻转动力学，以及各种甘露型糖中的参与事件本身。因此，该研究提供了甘露糖基二氧阴离子形成的完整图景。

附：英文原文

Title: Mechanism of C-3 Acyl Neighboring Group Participation in Mannuronic Acid Glycosyl Donors

Author: Frank F. J. de Kleijne, Peter H. Moons, Floor ter Braak, Hero R. Almizori, Luuk J. H. Jakobs, Kas J. Houthuijs, Giel Berden, Jonathan Martens, Jos Oomens, Floris P. J. T. Rutjes, Paul B. White, Thomas J. Boltje

Issue&Volume: December 18, 2024

Abstract: One of the main challenges in oligosaccharide synthesis is the stereoselective introduction of the glycosidic bond. In order to understand and control glycosylation reactions, thorough mechanistic studies are required. Reaction intermediates found by NMR spectroscopy often cannot explain the glycosylation’s stereochemical outcome. Hence, reactions may proceed through low-abundance reaction intermediates that are difficult to detect, according to a Curtin–Hammett scenario. We have previously observed that manno-type sugars can engage in C-3 acyl neighboring group participation. Herein, we report the detection of glycosyl dioxanium ions that result from C-3 neighboring group participation in mannuronic acid donors. Using a suite of exchange NMR techniques, we were able to dissect the kinetics of the conformational ring-flip that precedes C-3 acyl participation and the participation event itself in various manno-type sugars. Hence, this study provides a complete picture of mannosyl dioxanium ion formation.

DOI: 10.1021/jacs.4c13910

Source: https://pubs.acs.org/doi/full/10.1021/jacs.4c13910