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 chemoselectivities^3,4. 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.

低聚糖在整个生物学中具有多种功能。 ^1,2 为了研究这些功能，需要对这些结构复杂的分子进行多步化学合成。由于具有密集的立体中心和羟基，通过 O-糖基化组装寡糖需要同时控制位点选择性、立体选择性和化学选择性 ^3,4 。化学家传统上依靠保护基团操作来达到此目的， ^5–8 增加了大量的合成工作。在这里，我们报告了一个糖基化平台，该平台能够在未受保护或最低程度保护的供体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产生1,2-顺式-O-糖苷。烯丙基糖基砜的自由基活化 ⁹ 形成糖基溴。设计的氨基硼酸催化剂通过非共价氢键和可逆共价 B-O 键相互作用网络使这种反应中间体靠近受体，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。该方法适用于多种糖类型，适合制备天然存在的糖链和含有 11 个游离羟基的五糖。实验和计算研究提供了对选择性结果起源的见解。