Alkali-metal hexamethyldisilazide initiated polymerization on alpha-amino acid N-substituted N-carboxyanhydrides for facile polypeptoid synthesis

Polypeptoids have been explored as mimics of polypeptides, owing to polypeptoids' superior stability upon proteolysis. Polypeptoids can be synthesized from one-pot ring-opening polymerization of amino acid N-substituted N-carboxyanhydrides (NNCAs). However, the speed of polymerization of NNCAs can be very slow, especially for NNCAs bearing a bulky N-substitution group. This hindered the exploration on polypeptoids with more diverse structures and functions. Therefore, it is in great need to develop advanced strategies that can accelerate the polymerization on inactive NNCAs. Hereby, we report that lithium/sodium/potassium hexamethyldisilazide (Li/Na/KHMDS) initiates a substantially faster polymerization on NNCAs than do commonly used amine initiators, especially for NNCAs with bulky N substitution group. This fast NNCA polymerization will increase the structure diversity and application of polypeptoids as synthetic mimics of polypeptides. (c) 2021 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

Automated summary

The study demonstrates that lithium/sodium/potassium hexamethyldisilazide can initiate polymerization on NNCAs at a substantially faster rate, especially for NNCAs with bulky N substitution groups. This accelerated polymerization can increase the structural diversity and applications of polypeptoids as synthetic mimics of polypeptides.