Primary Amine and Solvent‐Induced Polymerizations of L‐ or D,L‐Phenylalanine N‐Carboxyanhydride

Abstract

Summary: Benzylamine, hexylamine and aniline‐initiated polymerizations of D,L‐phenylalanine and L‐phenylalanine N‐carboxyanhydride (D,L‐Phe‐NCA and L‐Phe‐NCA) were performed in various solvents. The isolated polypeptides were characterized by MALDI‐TOF mass spectroscopy. Exclusively linear polypeptides having one amide and one amino endgroup were found, when the polymerizations were conducted in a closed reaction vessel with dioxane or sulfolane as reaction media. Traces of water competed with aniline as initiator, when the reaction vessel was closed with a drying tube. In N,N‐dimethylformamide (DMF) formyl endgroups were formed at polymerization temperatures of 60 °C. In DMF and N‐methylpyrrolidone, cyclic oligo‐ and polypeptides were formed by a solvent‐induced polymerization initiated by zwitterions, which may compete with the primary amine‐initiated polymerizations.MALDI‐TOF mass spectrum of a poly(D,L‐phenylalanine) polymerized in NMP without addition of an initiator.magnified imageMALDI‐TOF mass spectrum of a poly(D,L‐phenylalanine) polymerized in NMP without addition of an initiator.

Revolutionary phosgene‐free synthesis of α‐amino acid N‐carboxyanhydrides using diphenyl carbonate based on activation of α‐amino acids by converting into imidazolium salts

“…NCA 3a was stable even in the presence of water, if the medium was enough acidified. The melting point of the obtained phenylalanine NCA was 89.1-90.4 C, which was in good agreement with the reported one (88-90 C) 24 to confirm the high purity of the obtained NCA.…”

Polypeptides and 100 Years of Chemistry of α‐Amino Acid N‐Carboxyanhydrides

“…[68] Broad frequency distributions were also reported for poly(l-Phe). [69] They resemble the frequency distributions of polycondensates, which typically have PDs ! 2.0.…”

Cyclic polymers: Synthetic strategies and physical properties

“…110 Small fractions of cyclic oligopeptides may also be formed, when primary amine-initiated polymerizations of NCAs are conducted in DMF (a frequently used reaction medium). 111 Detailed studies of this phenomenon revealed that polar, nucleophilic solvents such as DMF, N-methyl pyrrolidone, or dimethyl sulfoxide catalyze polymerizations of NCAs, even in the absence of initiators. 112 The polymerization mechanism may have a zwitterionic character as formulated in Scheme 29, and for N-substituted NCAs (e.g., sarcosine NCA) an alternative mechanism does not exist.…”