A facile glovebox-free strategy to significantly accelerate the syntheses of well-defined polypeptides by -carboxyanhydride (NCA) ring opening polymerizations.

A facile N flow-accelerated -carboxyanhydride ring opening polymerization (NCA ROP) is demonstrated, herein, with rigorous kinetic studies to evaluate the methodology in detail. By using -hexylamine as initiator and γ-benzyl-L-glutamate -carboxyanhydride (BLG-NCA) as monomer, the NCA ROP a normal amine mechanism (NAM) reached 90% conversion in 2 h under N flow at room temperature in a fume hood, much shorter than the time required for the same polymerization conducted in a glove box (14 h). The efficient removal of CO from the reaction by N flow drove the carbamic acid-amine equilibrium toward the formation of active nucleophilic amino termini and promoted polymerization. The detailed kinetic studies of the polymerization with different feed ratios and N flow rates were conducted, demonstrating the living feature of the NCA ROP and the tuning of the polymerization rate by simply changing the flow rate of N. Maintenance of the reactivity of the amino ω-chain terminus and control during a subsequent polymerization were confirmed by performing chain extension reactions. The N flow method provides a new straightforward strategy to synthesize well-defined polypeptides with predictable molecular weights and narrow molecular weight distributions (PDI < 1.19).