One-Step Synthesis for Orn-Val with High Molecular Weight and Low Polydispersity by Ugi Four-Component Condensation

Basic amino acid alternating copolymers exhibit exceptional antimicrobial properties and biosafety, yet their application is restricted by the complexity of the synthesis process and low molecular weight (<i>M</i>_n = 1000). In this study, we synthesized a basic amino acid alternating copolymer (Orn-Val) in only one step by the Ugi four-component condensation (Ugi'4CC), achieving high molecular weight (<i>M</i>_n = 20,000) and narrow polydispersity (PDI ≤ 1.10). Furthermore, we observed that factors such as the feed ratio, reaction solvent, and pH significantly influenced the molecular weight and polydispersity of MPE-Orn-Val-Cbz. Moreover, the structure of potassium isocyanate also significantly affected the molecular weight and polydispersity of the products. And it was also demonstrated that the obtained Orn-Val demonstrated excellent antimicrobial properties and biocompatibility. Therefore, this method effectively addresses the limitations associated with the complex synthesis process and low molecular weight of amino acid alternating copolymers.