Accelerated Polypeptide Synthesis via N-Carboxyanhydride Ring Opening Polymerization in Continuous Flow

Jeroen Hendrik Vrijsen, Alicia Rasines Mazo, Tanja Junkers, Greg Guanghua Qiao

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)


In nature, polypeptide-based materials are ubiquitous, yet their synthetic production is hampered by high cost, limited scalability, and often stringent reaction conditions. Herein an elegant approach is presented for N-carboxyanhydride ring opening polymerization (NCA ROP) of Nε-benzyloxycarbonyl-l-lysine (ZLL) and γ-benzyl-l-glutamate (BLG) NCA in continuous flow. The polymerization is initiated by primary amine initiators using N,N-dimethylformamide (DMF) as solvent. Carrying out the reaction in a silicon microflow reactor speeds up the rate of ROP (92% conversion in 40 min in flow as opposed to 6 h in batch) due to highly efficient permeation of CO2 through the reactor tubing. The polymerization strategy provides a facile, scale-up friendly alternative to traditional batch mode polymerization and has the capability of streamlining NCA ROP.

Original languageEnglish
Article number2000071
Number of pages6
JournalMacromolecular Rapid Communications
Issue number18
Publication statusPublished - 1 Sept 2020


  • continuous flow chemistry
  • flow polymerization
  • N-carboxyanhydride ring opening polymerization

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