Zweifel olefination for C-glycosylation

Abstract C-glycosides are significant in medicinal chemistry due to their resistance to enzymatic hydrolysis, making them more stable and bioavailable compared to O-glycosides. Their unique structure also offers potential for developing drugs with improved therapeutic properties, particularly in tre...

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Bibliographic Details
Main Authors: Florian Trauner, Bilel Boutet, Fabian Pilz, Verena Weber, Dorian Didier
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Communications Chemistry
Online Access:https://doi.org/10.1038/s42004-024-01339-4
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Summary:Abstract C-glycosides are significant in medicinal chemistry due to their resistance to enzymatic hydrolysis, making them more stable and bioavailable compared to O-glycosides. Their unique structure also offers potential for developing drugs with improved therapeutic properties, particularly in treating diseases like diabetes and cancer. The main challenge in synthesizing C-glycosides lies in forming the carbon-carbon bond between the sugar and aglycone efficiently, while controlling the stereochemistry and minimizing side reactions. Starting from glycal derivatives, the Zweifel olefination presents an elegant opportunity to access C-glycosides in a selective manner. α-Lithiation of D-glucal, L-rhamnal, D-xylal and L-arabinal scaffolds was employed as a starting point in the synthesis of corresponding unsaturated aryl-, heteroaryl- and alkenyl-C-glycosides. This provides a straightforward strategy towards pharmacorelevant gliflozins and other unreported rhamnal- and xylal-analogs.
ISSN:2399-3669