Solid-Phase Photochemical Peptide Homologation Cyclization

Org Lett. 2022 Jul 22;24(28):5176-5180. doi: 10.1021/acs.orglett.2c02012. Epub 2022 Jul 11.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclization
  • Esters*
  • Peptides* / chemistry


  • Esters
  • Peptides