N-Substituted Poly(α-amino acids). 1. Synthesis and Characterization of Poly(N-methyl-γ-methyl L-glutamate) and Poly(N-methyl-γ-ethyl L-glutamate)

Abstract

N-Substituted Poly(«-amino acids) 1041 stirring at 95 °C until it became homogeneous. This required less than 1 h. Freshly cut sodium metal (0.40 g, 0.018 mol) was then added, and the resulting pink reaction mixture was heated at 95 °C and stirred for 1.5 h. Approximately one-half of the excess phenol was then removed by vacuum distillation. The concentrated reaction mixture was allowed to cool to 40 °C and concentrated HC1 (10 mL) was added, slowly, with stirring. The resulting suspension was poured into 20 volumes of methanol to precipitate the polymer, which was then washed with methanol and dried in vacuo. The yield was 0.54 g. Most of this sample was rephenylated, using the procedure described above, but a portion of it was reprecipitated from acetone into methanol, and then dried in vacuo. The infrared spectrum of this portion contained a strong absorption band at 1702 cm4. A portion of this sample was methylated with diazomethane.1 The NMR spectrum of the resulting product contained a strong resonance at ~3.5. Its intensity indicated that approximately 11.5% of the units were methyl methacrylate units.

Convenient synthetic approach to poly(N‐Methyl L‐alanine) through polycondensation of activated urethane derivative of N‐methyl L‐alanine

“…The circular dichroism (CD) spectra of PNMA was also conducted in the aqueous and TFE solution, where the negative Cotton peak at 220–225 nm was observed, indicating formation of a right‐handed helix structure from all‐trans peptide configurations (Supporting Information Fig. S4), that agree with N ‐methylated polypeptides produced by solid‐state synthesis or NCA polymerization in the literature …”

“…These polypeptoids have been anticipated to be used as a drug delivery carrier, and construction of antifouling surface . N ‐Substituted polypeptide with substitution group at α‐carbon and amide nitrogen such as poly( N ‐methyl L‐alanine) (PNMA) has an additional feature for the conformation, that is well‐defined secondary structure based on all‐trans peptide configurations . For example, Imanishi et al reported the effect of N ‐substituted polypeptide on the polymerization of NCA as polymer catalysts using these features …”

Polypeptoids: A perfect match for molecular definition and macromolecular engineering?

“…Substitution of the nitrogen atom also strongly influences the solubility of oligo‐ and polypeptides . Interestingly, however, the water sorption in polyamides can be decreased by incorporation of N‐methylated polyamide …”

Insight into the synthesis of N-methylated polypeptides

“…As an alternative route for the preparation of poly(N-methyl-γ-methyl-L-glutamate) and poly(N-methylγ-ethyl-L-glutamate), they tested different methylation methods on poly(γ-methyl-L-glutamate) or poly(γ-ethyl-L-glutamate). 24 Like poly(N-methyl-L-alanine), both polymers were found to form a right-handed helix in a TFE solution of remarkably high stability, which retained their conformation even in pure TFA as observed by CD (circular dichroism) measurements. 25 A special case is the amino acid proline, the only proteinogenic amino acid containing a secondary amine.…”