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Solid-Phase Photochemical Peptide Homologation Cyclization

Michael Elbaum, Mahmoud A. Elkhalifa, Gary A. Molander, David M. Chenoweth

2022Organic Letters11 citationsDOIOpen Access PDF

Abstract

Forging new C(sp3)–C(sp3) bonds to central positions within a peptide backbone is critical for the development of new therapeutics and chemical probes. Currently, there are no methods for decarboxylating Asp and Glu side chains solid-phase photochemically or using such radicals to form peptide macrocycles. Herein, electron-donor-acceptor complexes between Hantzsch ester and on-resin peptide N-hydroxyphthalimide radical precursors are used to access these radicals, demonstrated with two-carbon homologations and homologation cyclizations of Atosiban and RGDf.

Topics & Concepts

ChemistryRadicalPeptidePhotochemistryAcceptorPhase (matter)Combinatorial chemistrySide chainStereochemistryOrganic chemistryBiochemistryCondensed matter physicsPhysicsPolymerChemical Synthesis and AnalysisRadical Photochemical ReactionsFluorine in Organic Chemistry
Solid-Phase Photochemical Peptide Homologation Cyclization | Litcius