Xie Demeng, Zeng Wei, Yang Jian, Ma Xiaofeng
Natural Products Research Center, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Nat Commun. 2024 Oct 24;15(1):9187. doi: 10.1038/s41467-024-53563-0.
C-Glycosides are essential for the study of biological processes and the development of carbohydrate-based drugs. Despite the tremendous hurdles, glycochemists have often fantasized about the efficient, highly stereoselective synthesis of C-glycosides with the shortest steps under mild conditions. Herein, we report a desulfurative radical protocol to synthesize C-alkyl glycosides and coumarin C-glycosides under visible-light induced conditions without the need of an extra photocatalyst, in which stable and readily available glycosyl thiols that could be readily obtained from native sugars are activated in situ by pentafluoropyridine. The benefits of this procedure include high stereoselectivity, broad substrate scope, and easy handling. Mechanistic studies indicate that the in situ produced tetrafluoropyridyl S-glycosides form key electron donor-acceptor (EDA) complexes with Hantzsch ester (for C-alkyl glycosides) or EtN (for coumarin C-glycosides), which, upon irradiation with visible light, trigger a cascade of glycosyl radical processes to access C-glycosides smoothly.
C-糖苷对于生物过程的研究以及基于碳水化合物的药物开发至关重要。尽管存在巨大障碍，但糖化学家常常幻想在温和条件下以最短步骤高效、高立体选择性地合成C-糖苷。在此，我们报道了一种脱硫化自由基方法，可在可见光诱导条件下合成C-烷基糖苷和香豆素C-糖苷，无需额外的光催化剂，其中可从天然糖轻松获得的稳定且易于制备的糖基硫醇通过五氟吡啶原位活化。该方法的优点包括高立体选择性、广泛的底物范围和易于操作。机理研究表明，原位生成的四氟吡啶基S-糖苷与汉斯酯（用于C-烷基糖苷）或EtN（用于香豆素C-糖苷）形成关键的电子供体-受体（EDA）络合物，在可见光照射下，引发一系列糖基自由基过程，从而顺利获得C-糖苷。
