Bacterial cell‐surface polysaccharides are involved in various biological processes and have attracted widespread attention as potential targets for developing carbohydrate‐based drugs. However, the accessibility of structurally well‐defined polysaccharide or related active oligosaccharide domains remains challenging. Herein, we describe an efficiently stereocontrolled approach for the first total synthesis of a unique pentasaccharide repeating unit containing four difficult‐to‐construct 1,2‐cis‐glycosidic linkages from the cell wall polysaccharide of Cutibacterium acnes C7. The features of our approach include: 1) acceptor‐reactivity‐controlled glycosylation to stereoselectively construct two challenging rare 1,2‐cis‐ManA2,3(NAc)2 (β‐2,3‐diacetamido‐2,3‐dideoxymannuronic acid) linkages, 2) combination use of 6‐O‐tert‐butyldiphenylsilyl (6‐O‐TBDPS)‐mediated steric shielding effect and ether solvent effect to stereoselectively install a 1,2‐cis‐glucosidic linkage, 3) bulky 4,6‐di‐O‐tert‐butylsilylene (DTBS)‐directed glycosylation to stereospecifically construct a 1,2‐cis‐galactosidic linkage, 4) stereoconvergent [2+2+1] and one‐pot chemoselective glycosylation to rapidly assemble the target pentasaccharide. Immunological activity tests suggest that the pentasaccharide can induce the production of proinflammatory cytokine TNF‐α in a dose‐dependent manner.

中文翻译：

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痤疮皮肤杆菌 C7 细胞壁多糖中独特五糖的受体反应控制立体会聚合成及其免疫活性

细菌细胞表面多糖参与多种生物过程，作为开发碳水化合物药物的潜在靶点而引起了广泛关注。然而，结构明确的多糖或相关活性寡糖结构域的可及性仍然具有挑战性。在此，我们描述了一种有效的立体控制方法，用于首次全合成独特的五糖重复单元，该单元包含来自痤疮皮肤杆菌 C7 细胞壁多糖的四个难以构建的 1,2-顺式糖苷键。我们方法的特点包括：1）受体反应性控制的糖基化立体选择性地构建两个具有挑战性的稀有1,2-顺式-ManA2,3(NAc)2（β-2,3-二乙酰氨基-2,3-二脱氧甘露糖醛酸）连接，2) 结合使用 6-O-叔丁基二苯基甲硅烷基 (6-O-TBDPS) 介导的空间屏蔽效应和醚溶剂效应来立体选择性地安装 1,2-顺式糖苷键，3) 大体积的 4,6-二-O-叔丁基亚甲硅基（DTBS）定向糖基化立体特异性地构建1,2-顺式半乳糖苷键，4）立体会聚[2+2+1]和一锅化学选择性糖基化以快速组装目标五糖。免疫活性测试表明，五糖可以以剂量依赖性方式诱导促炎细胞因子TNF-α的产生。