de Kleijne Frank F J, Moons Peter H, Ter Braak Floor, Almizori Hero R, Jakobs Luuk J H, Houthuijs Kas J, Berden Giel, Martens Jonathan, Oomens Jos, Rutjes Floris P J T, White Paul B, Boltje Thomas J
Department of Synthetic Organic Chemistry, Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, Nijmegen 6525 AJ, The Netherlands.
FELIX Laboratory, Institute for Molecules and Materials, Radboud University, Toernooiveld 7, Nijmegen 6525 ED, The Netherlands.
J Am Chem Soc. 2025 Jan 8;147(1):932-944. doi: 10.1021/jacs.4c13910. Epub 2024 Dec 18.
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.
寡糖合成中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，需要进行深入的机理研究。通过核磁共振光谱发现的反应中间体往往无法解释糖基化的立体化学结果。因此，根据柯廷-哈米特原理，反应可能通过难以检测的低丰度反应中间体进行。我们之前观察到甘露糖型糖可参与C-3酰基邻基参与作用。在此，我们报告了由C-3邻基参与甘露糖醛酸供体而产生的糖基二氧鎓离子的检测。使用一套交换核磁共振技术，我们能够剖析在各种甘露糖型糖中C-3酰基参与之前的构象环翻转动力学以及参与事件本身。因此，这项研究提供了甘露糖基二氧鎓离子形成的完整情况。
