Singlet Oxygen Photooxidation of Peptidic Oxazoles and Thiazoles

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 (O-1(2)); therefore, we designed and synthesized model oxazole- and thiazole-peptides and measured their O-1(2) 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 O-1(2) bimolecular reaction rate constant for a RiPP, the thiazole-containing peptide Aerucyclamide A, was measured and found in good agreement with the model peptides rate constant, highlighting the potential of using model peptides to study the transformations of other environmentally relevant NRPs and RiPPs.