Singlet Oxygen Photooxidation of Peptidic Oxazoles and Thiazoles

J Org Chem. 2019 Mar 1;84(5):2439-2447. doi: 10.1021/acs.joc.8b02684. Epub 2019 Feb 14.

Abstract

Oxazoles and thiazoles are commonly found moieties in nonribosomal peptides (NRPs) and ribosomally synthesized post-translationally modified peptides (RiPPs), which are important biomolecules present in the environment and in natural waters. From previous studies, they seem susceptible to oxidation by singlet oxygen (1O2); therefore, we designed and synthesized model oxazole- and thiazole-peptides and measured their 1O2 bimolecular reaction rate constants, showing slow photooxidation under environmental conditions. We reasoned their stability through the electron-withdrawing effect of the carboxamide substituent. Reaction products were elucidated and support a reaction mechanism involving cycloaddition followed by a series of rearrangements. The first 1O2 bimolecular reaction rate constant for a RiPP, the thiazole-containing peptide Aerucyclamide A, was measured and found in good agreement with the model peptide's rate constant, highlighting the potential of using model peptides to study the transformations of other environmentally relevant NRPs and RiPPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Kinetics
  • Oxazoles / chemical synthesis
  • Oxazoles / chemistry*
  • Oxidation-Reduction
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Peptides, Cyclic / chemistry
  • Photochemical Processes
  • Singlet Oxygen / chemistry*
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry*
  • Valine / chemistry

Substances

  • Oxazoles
  • Peptides
  • Peptides, Cyclic
  • Thiazoles
  • aerucyclamide A
  • Singlet Oxygen
  • Valine