Contribution from the chirality of the growing chain to the enantiomer selectivity in activated‐NCA polymerization of α‐amino acid N‐carboxyanhydride

Abstract

SynopsisAs a model compound for the growing chain in the activated-NCA type of polymerization of a-amino acid N-carboxyanhydride (NCA), 3-[w-acetylglycyl-poly(cu-amino acid) acylla-amino acid NCA (called the prepolymer) having various degrees of polymerization (DPs) was synthesized by the polymerization of Phe, Val, Glu(OEt), and Asp(0Bzl) NCA in the presence of AcGly NCA by the tertiary amine. Activated (S)-Phe, Val, Glu(OEt), and Asp(0Bzl) NCA were added to the terminal cyclic group of the corresponding (S)-or (R)-prepolymer, and the enantiomer selectivity in the reaction was investigated. With prepolymers having DPs ranging from 1 to 15, the addition reaction always took place preferentially between species having the same configuration, and the degree of the enantiomer selection increased with increasing D P of the prepolymer. With prepolymers having D P = 1 and 2, we found contributions from the chiral terminal unit and the chiral penultimate unit to the enantiomer selection, respectively. Prepolymer having D P = 5 was shown to take a &type conformation, which led to higher enantiomer selection; and prepolymers having DP = 10 and 15 were shown to take an a-helix conformation, which led to much higher enantiomer selection than did the P-type conformation. In the present investigation the mechanisms of terminal-unit control, penultimate-unit control, and conformational control of the enantiomer selection in the activated-NCA type of polymerization were clearly observed.

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

“…Therefore, these experiments did not give a clear cut answer. [340] However, experiments of Japanese authors [341] with optically active hydantoins as initiators of NCA polymerizations demonstrated that formation of homochiral sequences was favored. When mixtures of d-and lamino acids and CDI were polymerized in water, the resulting oligopeptides contained short homochiral blocks of either dor l-units that can form a b-sheet structure.…”