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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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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author Florian Trauner
Bilel Boutet
Fabian Pilz
Verena Weber
Dorian Didier
author_facet Florian Trauner
Bilel Boutet
Fabian Pilz
Verena Weber
Dorian Didier
author_sort Florian Trauner
collection DOAJ
description 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.
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institution Kabale University
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publishDate 2024-12-01
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spelling doaj-art-72ffa0b14dcc496aaba5b0f1912dd9f42024-12-22T12:19:56ZengNature PortfolioCommunications Chemistry2399-36692024-12-017111010.1038/s42004-024-01339-4Zweifel olefination for C-glycosylationFlorian Trauner0Bilel Boutet1Fabian Pilz2Verena Weber3Dorian Didier4Technische Universität Darmstadt, Clemens-Schöpf-Institut für Organische Chemie und BiochemieTechnische Universität Darmstadt, Clemens-Schöpf-Institut für Organische Chemie und BiochemieLudwig-Maximillians Universität, Department ChemieInstitute for Neuroscience and Medicine and Institute for Advanced Simulations (INM-9/IAS-5), Computational Biomedicine, Forschungszentrum JülichTechnische Universität Darmstadt, Clemens-Schöpf-Institut für Organische Chemie und BiochemieAbstract 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.https://doi.org/10.1038/s42004-024-01339-4
spellingShingle Florian Trauner
Bilel Boutet
Fabian Pilz
Verena Weber
Dorian Didier
Zweifel olefination for C-glycosylation
Communications Chemistry
title Zweifel olefination for C-glycosylation
title_full Zweifel olefination for C-glycosylation
title_fullStr Zweifel olefination for C-glycosylation
title_full_unstemmed Zweifel olefination for C-glycosylation
title_short Zweifel olefination for C-glycosylation
title_sort zweifel olefination for c glycosylation
url https://doi.org/10.1038/s42004-024-01339-4
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