Facile Route for the Synthesis of Adamantane‐Containing Polypeptides through Polycondensation of Activated Urethane Derivative of α‐Amino Acids

Abstract

A facile route has been discovered for the synthesis of polypeptides containing adamantane moieties in the side chain, poly(Nδ‐adamantyl‐l‐glutamine) P1 and poly(Nγ‐adamantyl‐l‐asparagine) P2, through polycondensation of an N‐phenoxycarbonyl derivative of the corresponding Nδ‐adamantyl‐l‐glutamine 1 and Nγ‐adamantyl‐l‐asparagine 2, respectively, along with the elimination of phenol and CO2. The urethane derivatives are readily synthesized by the N‐carbamylation of tetrabutylammonium salts of α‐amino acids with diphenyl carbonate. Polycondensation of the urethane derivative proceeds smoothly upon heating to 60 °C in N,N‐dimethylacetamide using n‐butylamine (n‐BuNH2) as an initiator. Size exclusion chromatography, 1H NMR spectra, and matrix‐assisted laser desorption/ionization time‐of flight mass spectrometry analyses reveal that polycondensation of 1 with n‐BuNH2 yields a well‐defined polypeptide in terms of molecular weight and terminal structure. On the other hand, polycondensation of 2 affords poor molecular weight control and leads to the formation of oligopeptides. Furthermore, using amine‐terminated poly(ethylene‐glycol) in place of n‐BuNH2 yields a diblock copolymer composed of polyether and polypeptide segments bearing an adamantane moiety through polycondensation of the urethane derivative. image