Pd-Catalyzed Stereospecific Glycosyl Cross-Coupling of Reversed Anomeric Stannanes for Modular Synthesis of Nonclassical C‑Glycosides  

作　　者：Guoqiang Cheng Bo Yang Yang Han Wei Lin Siyuan Tao Yong Nian Yingzi Li Maciej A.Walczak Feng Zhu 

机构地区：[1]Frontiers Science Center for Transformative Molecules(FSCTM),Center for Chemical Glycobiology,Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs,Department of Chemical Biology,School of Chemistry and Chemical Engineering,Zhangjiang Institute for Advanced Study,Shanghai Jiao Tong University,Shanghai 200240,P.R.China [2]School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing,Jiangsu 210023,P.R.China [3]Institute of Chemical Research of Catalonia(ICIQ),43007 Tarragona,Spain [4]Department of Chemistry,University of Colorado Boulder,Boulder,Colorado 80309,United States

出　　处：《Precision Chemistry》2024年第11期587-599,共13页精准化学（英文）

基　　金：sponsored by the National Key R&D Program of China(Grant No.2023YFA1508800);National Science Foundation(Grant No.22301178);Shanghai Pilot Program for Basic Research-Shanghai Jiao Tong University(Grant No.21TQ1400210);Fundamental Research Funds for the Central Universities(Grant No.22X010201631);the Open Grant from the Pingyuan Laboratory(2023PY-OP-0102);Excellent Young Scientists Fund Program(Overseas),Natural Science Founda-tion of Shanghai(Grant No.21ZR1435600);Shanghai Sailing Program(Grant No 21YF1420600);start-up fundings from Shanghai Jiao Tong University(SJTU);Part of this study was supported by the National Science Foundation(Grant No.82204192 to Y.N.);National Key R&D Program of China(Grant No.2023YFC2308200 to Y.N.);Natural Science Foundation of Jiangsu Province(BK20220471 to Y.N.);Beatriu de Pinós programme from AGAUR(Grant No.2022 BP 00055 to Y.L);the China Postdoctoral Science Foundation(2022M722071 to B.Y.).

摘　　要：Nonclassical C-glycosides,distinguished by their unique glycosidic bond connection mode,represent a promising avenue for the development of carbohydrate-based drugs.However,the accessibility of nonclassical C-glycosides hinders broader investigations into their structural features and modes of action.Herein,we present the first example of Pd-catalyzed stereospecific glycosylation of nonclassical anomeric stannanes with aryl or vinyl halides.This method furnishes desired nonclassical aryl and vinyl C-glycosides in good to excellent yields,while allowing for exclusive control of nonclassical anomeric configuration.Of significant note is the demonstration of the generality and practicality of this nonclassical C-glycosylation approach across more than 50 examples,encompassing various protected and unprotected saccharides,deoxy sugars,oligopeptides,and complex molecules.Furthermore,biological evaluation indicates that nonclassical C-glycosylation modifications of drug molecules can positively impact their biological activity.Additionally,extensive computational studies are conducted to elucidate the rationale behind differences in reaction reactivity,unveiling a transmetalation transition state containing silver(Ag)within a six-membered ring.Given its remarkable controllability,predictability,and consistently high chemical selectivity and stereospecificity regarding nonclassical anomeric carbon and Z/E configuration,the method outlined in this study offers a unique solution to the longstanding challenge of accessing nonclassical C-glycosides with exclusive stereocontrol.

关 键 词：Glycosylation CROSS-COUPLING Nonclassical C-glycosides Reversed anomeric stannanes STEREOSPECIFICITY 

分 类 号：O63[理学—高分子化学]