TY - JOUR
T1 - Diastereoselective Synthesis of Aryl C-Glycosides from Glycosyl Esters via C−O Bond Homolysis
AU - Wei, Yongliang
AU - Ben-zvi, Benjamin
AU - Diao, Tianning
N1 - Publisher Copyright:
© 2021 Wiley-VCH GmbH
PY - 2021/4/19
Y1 - 2021/4/19
N2 - C-aryl glycosyl compounds offer better in vivo stability relative to O- and N-glycoside analogues. C-aryl glycosides are extensively investigated as drug candidates and applied to chemical biology studies. Previously, C-aryl glycosides were derived from lactones, glycals, glycosyl stannanes, and halides, via methods displaying various limitations with respect to the scope, functional-group compatibility, and practicality. Challenges remain in the synthesis of C-aryl nucleosides and 2-deoxysugars from easily accessible carbohydrate precursors. Herein, we report a cross-coupling method to prepare C-aryl and heteroaryl glycosides, including nucleosides and 2-deoxysugars, from glycosyl esters and bromoarenes. Activation of the carbohydrate substrates leverages dihydropyridine (DHP) as an activating group followed by decarboxylation to generate a glycosyl radical via C−O bond homolysis. This strategy represents a new means to activate alcohols as a cross-coupling partner. The convenient preparation of glycosyl esters and their stability exemplifies the potential of this method in medicinal chemistry.
AB - C-aryl glycosyl compounds offer better in vivo stability relative to O- and N-glycoside analogues. C-aryl glycosides are extensively investigated as drug candidates and applied to chemical biology studies. Previously, C-aryl glycosides were derived from lactones, glycals, glycosyl stannanes, and halides, via methods displaying various limitations with respect to the scope, functional-group compatibility, and practicality. Challenges remain in the synthesis of C-aryl nucleosides and 2-deoxysugars from easily accessible carbohydrate precursors. Herein, we report a cross-coupling method to prepare C-aryl and heteroaryl glycosides, including nucleosides and 2-deoxysugars, from glycosyl esters and bromoarenes. Activation of the carbohydrate substrates leverages dihydropyridine (DHP) as an activating group followed by decarboxylation to generate a glycosyl radical via C−O bond homolysis. This strategy represents a new means to activate alcohols as a cross-coupling partner. The convenient preparation of glycosyl esters and their stability exemplifies the potential of this method in medicinal chemistry.
KW - C-glycosylation
KW - cross-coupling
KW - glycosyl radicals
KW - nucleoside analogues
KW - photoredox
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U2 - 10.1002/anie.202014991
DO - 10.1002/anie.202014991
M3 - Article
C2 - 33438338
AN - SCOPUS:85102333696
SN - 1433-7851
VL - 60
SP - 9433
EP - 9438
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 17
ER -