Solid-Phase Photochemical Peptide Homologation Cyclization.

Forging new C(sp 3 )-C(sp 3 ) 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.