Palladium-Catalyzed Synthesis of Cyclophane-Braced Peptide Macrocycles
Construction of Natural-Product-Like Cyclophane-Braced Peptide Macrocycles via sp3 C–H Arylation.
J. Am. Chem. Soc. 2019;
20 August 2019 (online)
Key wordspalladium catalysis - cyclophanes - peptide macrocycles - arylation - picolinamides - directing groups
Cyclic peptides possess great potential for modulating challenging biological processes. The authors have developed a general method for the synthesis of cyclophane-braced peptide macrocycles through palladium-catalyzed C(sp3)–H arylation.
Cyclophane motifs with unusual structural and stereochemical complexity were obtained by the picolinamide-directed intramolecular γ-selective C(sp3)–H arylation of the N-termini of peptide substrates at both the methyl and methylene positions.