Cyclic Polypeptides by Solvent-Induced Polymerizations of α-Amino Acid N-Carboxyanhydrides

Solutions of dl -phenylalanine-NCA in eight different solvents were thermostated at 20 °C for 4 days (and in two cases at 60 °C) without addition of initiators. Spontaneous polymerizations were observed in dimethylformamide (DMF), in N -methylpyrrolidone (NMP), and in dimethyl sulfoxide (DMSO). In dimethyl sulfoxide also sarcosine-NCA, l -alanine-NCA, d, l -leucine-NCA, and dl -valine-NCA underwent spontaneous polymerizations. However, in N -methylpyrrolidone, only sarcosine-NCA and l -alanine-NCA polymerized. The products of all these solvent-induced polymerizations were identified by MALDI−TOF mass spectrometry as cyclic oligo- and polypeptides. This fact and the finding that only the most nucleophilic solvents induce spontaneous polymerizations indicate a zwitterionic polymerization mechanism.