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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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N‐Alkylated Analogues of Indolylthio Glycosides as Glycosyl Donors with Enhanced Activation Profile
Abstract While studying indolylthio glycosides, previously we determined their activation profile that required large excess of activators. This drawback was partially addressed in the present study of N‐alkylated SInR derivatives. The activation process was studied by NMR and the increased understanding of the mechanism led to a discovery of different activation pathways taking place with SIn versus SInR derivatives. Also investigated was orthogonality of the SInR leaving groups versus thioglycosides and selective activation of thioimidates over SInR glycosides.
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- PAR ID:
- 10412782
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- European Journal of Organic Chemistry
- Volume:
- 2022
- Issue:
- 18
- ISSN:
- 1434-193X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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