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DOI: 10.1055/a-2601-5296
Racemization- and Epimerization-Free Stereoselective Synthesis of (Z)-Fluoroalkene-Type Peptidomimetics
Racemization-Free Peptide Bond Formation via 2-Nitrobenzenesulfonyl Strategy for Diastereoselective Synthesis of (Z)-Fluoroalkene-Type Peptidomimetics.
Org. Biomol. Chem. 2025;
23: 4480-4486
DOI: 10.1039/D5OB00477B
Keywords
racemization-free - epimerization-free - stereoselective synthesis - (Z)-fluoroalkenes - peptidomimetics - FADIs
Significance
Synthesis of fluoroalkene-type peptidomimetics has gained immense attention in medicinal chemistry. The authors discovered an innovative coupling strategy that effectively eliminates racemization and epimerization, allowing for the stereoselective synthesis of fluoroalkene-type peptidomimetics. By reacting Xaa-Pro-type FADIs with amino acid benzyl esters or peptides, this method takes advantage of the unique properties of the nosyl (2-nitrobenzenesulfonyl) group as an N-terminal protecting agent.
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Comment
This is a novel strategy for peptide bond formation that is free from racemization and epimerization, targeted at Xaa-Pro-type FADIs. This efficient method ensures high stereochemical fidelity in the synthesis of peptidomimetics. The use of the nosyl group promoted sulfonamide anion formation, thus successfully suppressing α-deprotonation and preserving stereochemistry.
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Publication History
Article published online:
23 June 2025
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