Stereoselective Synthesis of 2-Deoxy Glycosides via a Novel 2-O-Resided (o-Alkynyl)benzoate-Initiated 1,2-Sulfur Migration/Glycosylation and Desulfurization Protocol as well as Mechanism Elucidation
Corresponding Author
Jin-Xi Liao
National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang, Jiangxi, 330022 China
These authors contributed equally to this work.
E-mail: [email protected]; [email protected]Search for more papers by this authorZhen-Qiang Li
National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang, Jiangxi, 330022 China
These authors contributed equally to this work.
Search for more papers by this authorYanli Qiu
Shanghai Frontiers Science Center of TCM Chemical Biology, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203 China
These authors contributed equally to this work.
Search for more papers by this authorXiang-Yang Gao
National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang, Jiangxi, 330022 China
These authors contributed equally to this work.
Search for more papers by this authorXin Lv
National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang, Jiangxi, 330022 China
Search for more papers by this authorHui Liu
National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang, Jiangxi, 330022 China
Search for more papers by this authorYuan-Hong Tu
National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang, Jiangxi, 330022 China
Search for more papers by this authorCorresponding Author
Jian-Song Sun
National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang, Jiangxi, 330022 China
School of Life Science and Health Engineering, Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu, 214122 China
E-mail: [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Jin-Xi Liao
National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang, Jiangxi, 330022 China
These authors contributed equally to this work.
E-mail: [email protected]; [email protected]Search for more papers by this authorZhen-Qiang Li
National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang, Jiangxi, 330022 China
These authors contributed equally to this work.
Search for more papers by this authorYanli Qiu
Shanghai Frontiers Science Center of TCM Chemical Biology, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203 China
These authors contributed equally to this work.
Search for more papers by this authorXiang-Yang Gao
National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang, Jiangxi, 330022 China
These authors contributed equally to this work.
Search for more papers by this authorXin Lv
National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang, Jiangxi, 330022 China
Search for more papers by this authorHui Liu
National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang, Jiangxi, 330022 China
Search for more papers by this authorYuan-Hong Tu
National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang, Jiangxi, 330022 China
Search for more papers by this authorCorresponding Author
Jian-Song Sun
National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, 99 Ziyang Avenue, Nanchang, Jiangxi, 330022 China
School of Life Science and Health Engineering, Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu, 214122 China
E-mail: [email protected]; [email protected]Search for more papers by this authorComprehensive Summary
Stereoselective construction of 2-deoxy-glycosidic linkages has been achieved by the 1,2-sulfur migration/glycosylation and desulfurization strategy; however, current protocols suffer from harsh reaction conditions and unsatisfactory stereoselectivity, particularly during the 1,2-S-migration/glycosylation step. With 2-O-resided (o-alkynyl)benzoate and anomeric p-methoxyphenylsulfenyl groups as the initiating and migrating groups, respectively, a novel protocol for the efficient synthesis of 2-deoxy-glycosides via the 1,2-sulfur migration/glycosylation-desulfurization strategy has been established, which is featured by the mild and catalytic reaction conditions, expanded substrate scope, as well as good to excellent diastereoselectivity. Mechanism studies determined hyperconjugation-stabilized oxocarbenium ion as the key intermediate, achieving high 1,2-trans stereocontrol through thermodynamic, steric, as well as electrostatic effects. This provides the fresh insight for the operative mechanism of the 1,2-sulfur migration/glycosylation and desulfurization strategy, further corroborated by the elaborately designed testing reactions and DFT calculations. Moreover, the synthetic potential of the newly established protocol was examined by the practical synthesis of natural product, culminating in the acquisition of digoxin from acetylated digoxigenin in 25% overall yield through an 8-step longest linear sequence.
Supporting Information
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Appendix S1: Supporting Information |
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