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Abstract C-Alkyl glycosides represent an attractive class of nonhydrolyzable carbohydrate mimetics which possess enormous potential as next-generation therapeutics. Methods for the direct stereoselective synthesis of C-alkyl glycosides with a broad substrate tolerance are limited, however. This is especially in the case of β-linked C-alkyl glycosides, where direct methods for synthesis from commonly available coupling partners remain limited. This Account describes the evolution of our laboratory’s studies on glycosyl sulfonate chemistry from a method for the construction of simple β-linked 2-deoxy-sugars to a technology for the direct synthesis of β-linked acyl and homoacyl glycosides that can be elaborated into more complex structures. 1 Introduction 2 Glycosyl Sulfonates 3 Glycosyl Sulfonates in Oligosaccharide Synthesis 4 Matching Donor and Sulfonate Reactivity 5 β-Linked C-Acyl and Homoacyl Glycoside Synthesis 6 Elaboration to other Products 7 Conclusion
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Diastereoselective Synthesis of Aryl C ‐Glycosides from Glycosyl Esters via C−O Bond Homolysis
Abstract C‐aryl glycosyl compounds offer better in vivo stability relative toO‐ andN‐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 ofC‐aryl nucleosides and 2‐deoxysugars from easily accessible carbohydrate precursors. Herein, we report a cross‐coupling method to prepareC‐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.
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- Award ID(s):
- 1827902
- PAR ID:
- 10221413
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 60
- Issue:
- 17
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 9433-9438
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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