On-Resin Selenopeptide Catalysts: Synthesis and Applications of Enzyme-Mimetic Reactions and Cyclization of Unsaturated Carboxylic Acids.

Selenium reagents are useful for selenoenzyme-mimicking reactions, as well as for organic synthesis. However, the reaction waste containing selenium frequently smells unpleasant and exhibits serious toxicity. Herein, we have developed new-type on-resin selenium reagents, H-UXX···-PAM () and Ac-(X)UXX···-PAM (), where U and U represent selenocysteine (U) and -methoxybenzyl (PMB)-protected U, respectively, as recyclable catalysts, in which U-containing peptide chains are linked to the polystyrene resin PAM. Synthesized on-resin selenopeptides - with a variable amino acid sequence were evaluated for their glutathione peroxidase (GPx)-like activity using the UV and H NMR methods, using the reaction between dithiothreitol (DTT) and HO in methanol. It was found that the intramolecular interaction between U and a basic amino acid residue, such as histidine (H) and lysine (K), enhances peroxidase activity through the formation of an NH···Se hydrogen bond. On the other hand, the catalytic activity of - was evaluated in the oxidative cyclization of β,γ-unsaturated acids () into α,β-unsaturated lactones (). Although the yield of was significantly decreased after second- or third-round reaction, due to detachment of the selenium moiety from the resin, the results demonstrated reusability, as well as a substrate scope of as a catalyst. Since U is a natural amino acid, on-resin selenopeptides are potential targets as novel-type green redox catalysts.