Organocatalysis by hydrogen-bonding: a new approach to controlled/living polymerization of alpha-amino acid N-carboxyanhydrides

A new method, based on hydrogen-bonding organocatalysis, was developed to achieve living ring-opening polymerization of N-carboxyanhydride of a-amino acids using aminoalcohols as initiators in the presence of N,N'-bis[3,5-bis(trifluoromethyl)phenyl]thiourea (TU-S). The thiourea provides, through hydrogen bonding, simultaneous activation of NCA monomers/reversible deactivation of polymer chainends/silencing of the tertiary amine and thus allows the polymerization to proceed in a highly controllable mode. For example, by using N, N-dimethyl ethanolamine (DMEA), as an initiator in the presence of TU-S, a series of well-defined linear polypeptides with differently designed M(n)s (3.01 x 10(4)-18.10 x 10(4)) and low PDI values (1.02-1.05) were successfully synthesized. This general strategy was also extended to the synthesis of well-defined di-and multi-armed polypeptides by using di-, tri-, or tetra-aminoalcohol initiators (methyldiethanolamine (MDEA), triethanolamine (TEA) or N, N, N', N'-tetrakis(2-hydroxyethyl)-ethylenediamine (THEED)) in the presence of TU-S.