C-Glycosides are important carbohydrate mimetics found in natural products,bioactive compounds,and marketed drugs.However,stereoselective preparation of this class of glycomimetics remains a significant challenge in o...C-Glycosides are important carbohydrate mimetics found in natural products,bioactive compounds,and marketed drugs.However,stereoselective preparation of this class of glycomimetics remains a significant challenge in organic synthesis.Herein,we report an excited-state palladium-catalyzedα-selective C-ketonylation synthetic strategy using readily available 1-bromosugars to access a range of C-glycosides.The reaction featured excellentα-selectivity and mild conditions that tolerated a wide range of functional groups and complex molecular architectures.The resultingα-ketonylsugars could serve as versatile precursors for theirβ-isomers and other C-glycosides.Preliminary experimental and computational studies of the mechanism suggested a radical pathway involving the formation of palladoradical and glycosyl radical that undergoes polarity-mismatched coupling with silyl enol ether,affording the desiredα-ketonylsugars.Insight into the reactivity and mechanism will inspire a new reaction development and provide straightforward access to bothα-andβ-C-glycosides,thereby greatly expanding the chemical and patent spaces of glycomimetics.展开更多
基金The research reported in this publication was supported by the National Institutes of Health(grant no.R35-GM119652 to M.-Y.N.and grant no.R35-GM128779 to P.L.)DFT calculations were performed at the Center for Research Computing at the University of Pittsburgh,PA,USA,the Texas Advanced Computing Center(TACC)Frontera supercomputer,TX,USA,and the Extreme Science and Engineering Discovery Environment(XSEDE),TX,USA,supported by the National Science Foundation,VA,USA,grant number ACI1548562The Shimadzu ultraperformance liquid chromatography/mass spectrometry(UPLC/MS)used for portions of this work were purchased with funds from the National Institute of General Medical Sciences(NIGMS,MD,USA)equipment administrative supplement(grant no.R35-GM119652-04S1),Shimadzu Scientific Instruments grant,and Office of the Vice President for Research at Stony Brook University,NY,USA.
文摘C-Glycosides are important carbohydrate mimetics found in natural products,bioactive compounds,and marketed drugs.However,stereoselective preparation of this class of glycomimetics remains a significant challenge in organic synthesis.Herein,we report an excited-state palladium-catalyzedα-selective C-ketonylation synthetic strategy using readily available 1-bromosugars to access a range of C-glycosides.The reaction featured excellentα-selectivity and mild conditions that tolerated a wide range of functional groups and complex molecular architectures.The resultingα-ketonylsugars could serve as versatile precursors for theirβ-isomers and other C-glycosides.Preliminary experimental and computational studies of the mechanism suggested a radical pathway involving the formation of palladoradical and glycosyl radical that undergoes polarity-mismatched coupling with silyl enol ether,affording the desiredα-ketonylsugars.Insight into the reactivity and mechanism will inspire a new reaction development and provide straightforward access to bothα-andβ-C-glycosides,thereby greatly expanding the chemical and patent spaces of glycomimetics.
