Catalytic glycosylation for minimally protected donors and acceptors

• 成果类型: Article
• 署名作者: Dang, Qiu-Di; Deng, Yi-Hui; Sun, Tian-Yu; Zhang, Yao; Li, Jun; Zhang, Xia; Wu, Yun-Dong; Niu, Dawen
• 署名单位: Sichuan University; Sichuan University; Peking University Shenzhen Graduate School (PKU Shenzhen); Peking University; Shenzhen Bay Laboratory
• 刊物名称: Nature
• ISSN/ISSBN: 0028-3932
• DOI: 10.1038/s41586-024-07695-4
• 发表日期: 2024-08-08
• 关键词: 1; 2-cis glycosylation; glycosidation; stereoselectivity; ion

摘要

Oligosaccharides have myriad functions throughout biological processes1,2. Chemical synthesis of these structurally complex molecules facilitates investigation of their functions. 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 purpose5-8, adding considerable 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 catalyst brings this reactive intermediate close to an acceptor through a network of non-covalent 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 the preparation of naturally occurring sugar chains and pentasaccharides containing 11 free hydroxyls. Experimental and computational studies provide insights into the origin of selectivity outcomes. A glycosylation platform is demonstrated that enables selective coupling between a wide range of unprotected or minimally protected donor and acceptor sugars, producing 1,2-cis-O-glycosides in a catalyst-controlled, site-selective manner.