Facile Preparation of Heteropolypeptides from Crude Mixtures of α-Amino Acid <i>N</i>-Carboxyanhydrides

Heteropolypeptides bearing two or more functional side chains are promising polymeric materials for various biomedical applications. However, conventional preparation of heteropolypeptides relies on the synthesis and purification of each <i>N</i>-carboxyanhydride (NCA) monomer in a separate manner, which substantially increases the time and cost. Herein, we report the facile preparation of heteropolypeptides with up to 86% yield within several hours, which are obtained from a mixture of crude NCA monomers. The combination of <i>n</i>-hexane precipitation and biphasic segregation effectively removed >90% impurities from crude NCA mixtures, allowing for the successful polymerization process. Various heteropolypeptides with monomodal distribution and narrow dispersity were efficiently prepared, whose compositions were predetermined by the feeding ratios of amino acids. We believe that this work significantly simplifies the preparation of various heteropolypeptides, boosting the downstream studies of these promising materials.