Zweifel olefination for C-glycosylation.
Florian Trauner1,2, Bilel Boutet1, Fabian Pilz2
1Technische Universität Darmstadt, Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Peter-Grünberg-Straße 4, 64287, Darmstadt, Germany.
Communications Chemistry
|December 21, 2024
Summary
C-glycoside synthesis is advanced using Zweifel olefination on glycal derivatives. This method efficiently creates carbon-carbon bonds for stable, bioavailable drug candidates like gliflozins.
Area of Science:
- Medicinal Chemistry
- Organic Synthesis
- Carbohydrate Chemistry
Background:
- C-glycosides offer enhanced stability and bioavailability over O-glycosides, crucial for drug development.
- Their therapeutic potential spans diseases like diabetes and cancer.
- Efficient synthesis of the C-glycosidic bond remains a key challenge.
Purpose of the Study:
- To develop a selective and efficient method for synthesizing C-glycosides.
- To explore the application of Zweifel olefination in C-glycoside synthesis.
- To access novel aryl-, heteroaryl-, and alkenyl-C-glycosides.
Main Methods:
- Utilizing glycal derivatives as starting materials.
- Employing α-lithiation of D-glucal, L-rhamnal, D-xylal, and L-arabinal scaffolds.
- Applying the Zweifel olefination reaction for C-C bond formation.
Main Results:
- Demonstrated a straightforward strategy for synthesizing unsaturated C-glycosides.
- Successfully synthesized aryl-, heteroaryl-, and alkenyl-C-glycosides.
- Provided access to pharmacorelevant gliflozins and novel rhamnal- and xylal-analogs.
Conclusions:
- Zweifel olefination offers an elegant and selective route to C-glycosides.
- This approach facilitates the synthesis of potentially valuable therapeutic agents.
- The method is applicable to various glycal scaffolds, expanding synthetic possibilities.
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