Ding Ya-Nan, Xu Mei-Ze, Huang Yan-Chong, Ackermann Lutz, Kong Xiangtao, Liu Xue-Yuan, Liang Yong-Min
State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, 222 South Tianshui Road, 730000, Lanzhou, Gansu Province, China.
Institut für Organische und Biomolekulare Chemie and Wöhler-Research Institute for Sustainable Chemistry (WISCh), Georg-August-Universität, Tammannstrasse 2, 37077, Göttingen, Germany.
Nat Commun. 2024 Mar 30;15(1):2794. doi: 10.1038/s41467-024-47060-7.
C-oligosaccharides are found in natural products and drug molecules. Despite the considerable progress made during the last decades, modular and stereoselective synthesis of C-oligosaccharides continues to be challenging and underdeveloped compared to the synthesis technology of O-oligosaccharides. Herein, we design a distinct strategy for the stereoselective and efficient synthesis of C-oligosaccharides via palladium-catalyzed nondirected C1-H glycosylation/C2-alkenylation, cyanation, and alkynylation of 2-iodoglycals with glycosyl chloride donors while realizing the difunctionalization of 2-iodoglycals. The catalysis approach tolerates various functional groups, including derivatives of marketed drugs and natural products. Notably, the obtained C-oligosaccharides can be further transformed into various C-glycosides while fully conserving the stereochemistry. The results of density functional theory (DFT) calculations support oxidative addition mechanism of alkenyl-norbornyl-palladacycle (ANP) intermediate with α-mannofuranose chloride and the high stereoselectivity of glycosylation is due to steric hindrance.
C-寡糖存在于天然产物和药物分子中。尽管在过去几十年中取得了相当大的进展，但与O-寡糖的合成技术相比，C-寡糖的模块化和立体选择性合成仍然具有挑战性且发展不足。在此，我们设计了一种独特的策略，通过钯催化的2-碘代糖与糖基氯供体的非定向C1-H糖基化/C2-烯基化、氰化和炔基化反应，实现2-碘代糖的双官能化，从而立体选择性地高效合成C-寡糖。该催化方法能够耐受各种官能团，包括市售药物和天然产物的衍生物。值得注意的是，所得到的C-寡糖可以进一步转化为各种C-糖苷，同时完全保留立体化学结构。密度泛函理论（DFT）计算结果支持烯基-降冰片基-钯环（ANP）中间体与α-甘露呋喃糖氯的氧化加成机理，糖基化的高立体选择性归因于空间位阻。
