PIDA-mediated synthesis of kynurenine derivatives by oxidative fragmentation of the tryptophan scaffold

Abstract

Kynurenine metabolites are derived from the aromatic amino acid, tryptophan, and their chemical synthesis has been sought to understand the tryptophan–kynurenine-based biochemical reactions that could provide opportunities for exploring therapeutic values. This report describes the synthesis of kynurenine (kyn) derivatives from tryptophan-containing peptides using the versatile hypervalent iodine reagent, phenyliodine(III)diacetate (PIDA), through the C–C bond fragmentation of tryptophan's indole ring. However, BocNH-Trp-OH and N-arylated (both benzenoid and non-benzenoid) tryptophan derivatives produce unique spirocyclic molecules with PIDA under similar reaction conditions. In screening for therapeutic values, the sequence-specific kynurenine derivatives show inhibition of quorum sensing against multidrug-resistant pathogenic bacteria, Pseudomonas aeruginosa PA14 strain.