四川大学钮大文团队报道了最低限度保护供体和受体的催化糖基化。相关研究成果于2024年6月17日发表在《自然》。

低聚糖在整个生物学中具有无数的功能。要研究这些功能，需要对这些结构复杂的分子进行多步化学合成。由于立体中心和羟基的浓度很高，通过O-糖基化组装寡糖需要同时控制位点、立体和化学选择性。传统上，化学家依靠保护基团操作来实现这一目的，增加了大量的合成工作。

该文中，研究人员报道了一种糖基化平台，该平台能够在未受保护或保护程度最低的供体糖和受体糖之间进行选择性偶联，以催化剂控制的位点选择性方式生产1,2-顺式-O-糖苷。烯丙基糖基砜基于自由基的活化形成糖基溴化物。设计的氨基硼酸催化剂通过非共价氢键和可逆共价B–O键相互作用的网络，使这种反应性中间体接近受体，从而实现精确的糖基转移。

不同的氨基硼酸催化剂可以通过影响其与底物的相互作用模式来切换糖基化位点。该方法适用于广泛的糖类型，适于制备天然存在的糖链和含有11个游离羟基的五糖。实验和计算研究为选择性结果的起源提供了见解。

附：英文原文

Title: Catalytic Glycosylation for Minimally Protected Donors and Acceptors

Author: Dang, Qiu-Di, Deng, Yi-Hui, Sun, Tian-Yu, Zhang, Yao, Li, Jun, Zhang, Xia, Wu, Yun-Dong, Niu, Dawen

Issue&Volume: 2024-06-17

Abstract: Oligosaccharides have myriad functions throughout biology.1,2 To investigate these functions requires multi-step chemical synthesis of these structurally complex molecules. With a dense concentration of stereocentres and hydroxyl groups, oligosaccharide assembly through O-glycosylation requires simultaneous control of site-, stereo-, and chemoselectivities3,4. Chemists have traditionally relied on protecting group manipulations for this purpose,5–8 adding a lot of synthetic work. Here, we report a glycosylation platform that enables selective coupling between unprotected or minimally protected donor and acceptor sugars, producing 1,2-cis-O-glycosides in a catalyst-controlled, site-selective manner. Radical-based activation9 of allyl glycosyl sulfones forms glycosyl bromides. A designed aminoboronic acid catalysts bring this reactive intermediate close to an acceptor through a network of noncovalent hydrogen bonding and reversible covalent B–O bonding interactions, allowing precise glycosyl transfer. The site of glycosylation can be switched with different aminoboronic acid catalysts by affecting their interaction modes with substrates. The method accommodates a wide range of sugar types, amenable to preparing naturally occurring sugar chains and pentasaccharides containing 11 free hydroxyls. Experimental and computational studies provide insights into the origin of selectivity outcomes.

DOI: 10.1038/s41586-024-07695-4

Source: https://www.nature.com/articles/s41586-024-07695-4