Sheng Xu, Yuanyuan Ping, Minghao Xu, Guozhen Wu, Yang Ke, Rui Miao, Xiaotian Qi, Wangqing Kong
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引用次数: 0
摘要
碳水化合物在药物化学和生物化学中发挥着重要作用。然而,它们的合成依赖于专门设计的糖基供体,这些供体通常不稳定,需要多步合成。此外,在糖环上催化和立体选择性地安装芳基化季铵盐立体中心仍然是一项艰巨的挑战。在此,我们报告了一种简便、多用途的方法,可从易于获得且稳定的 1-脱氧糖苷合成多种 C-R(其中 R 为芳基、杂芳基、烯基、炔基或烷基)糖苷。该反应在温和的条件下进行,在广泛的糖基单元范围内具有很高的立体选择性。该方案可用于合成具有挑战性的 2-脱氧糖苷、无保护糖苷、非经典糖苷和氘代糖苷。我们进一步开发了碳水化合物的催化剂控制位点发散官能化技术,用于合成现有方法无法合成的、含有芳基化季铵盐立体中心的各种未开发碳水化合物。在合成医药相关分子和碳水化合物时,进一步证明了这一策略的合成效用。
Stereoselective and site-divergent synthesis of C-glycosides
Carbohydrates play important roles in medicinal chemistry and biochemistry. However, their synthesis relies on specially designed glycosyl donors, which are often unstable and require multi-step synthesis. Furthermore, the catalytic and stereoselective installation of arylated quaternary stereocentres on sugar rings remains a formidable challenge. Here we report a facile and versatile method for the synthesis of diverse C–R (where R is an aryl, heteroaryl, alkenyl, alkynyl or alkyl) glycosides from readily available and bench-stable 1-deoxyglycosides. The reaction proceeds under mild conditions and exhibits high stereoselectivity across a broad range of glycosyl units. This protocol can be used to synthesize challenging 2-deoxyglycosides, unprotected glycosides, non-classical glycosides and deuterated glycosides. We further developed the catalyst-controlled site-divergent functionalization of carbohydrates for the synthesis of various unexplored carbohydrates containing arylated quaternary stereocentres that are inaccessible by existing methods. The synthetic utility of this strategy is further demonstrated in the synthesis of pharmaceutically relevant molecules and carbohydrates.
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