Primary ammonium/tertiary amine-mediated controlled ring opening polymerisation of amino acid N-carboxyanhydrides

Abstract

Stable commercial primary ammonium chlorides were combined with tertiary amines to initiate the controlled ring opening polymerisation of amino acid N-carboxyanhydrides to yield polypeptides with defined end group structure, predetermined molar mass and narrow molar mass distribution

Synthesis of polysarcosine from air and moisture stable N-phenoxycarbonyl-N-methylglycine assisted by tertiary amine base

“…FT-IR analyses confirmed the transformation of Poc-Sar into Sar-NCA, by the two characteristic vibration bands (NCA, CvO stretch) at ν = 1775 and 1850 cm −1 (ESI †). 26 As expected, the reaction was dramatically accelerated by the presence of TEA, and quantitative conversion of the Poc-Sar could be achieved within less than 8 hours (≥0.5 equiv. TEA) or 14 hours (0.2 equiv.…”

“…Ideally, the tertiary amine base does not initiate an uncontrolled polymerization of the Sar-NCA (which is a cyclic tertiary amide without acidic protons), which can only happen with an α-amino acid NCA (deprotonation of the NCA secondary amide and subsequent polymerization via the activated monomer mechanism). 13,26 Also, the released PhO − should be readily protonated (PhOH, pK a 18.0 (DMSO)) 25 by Poc-Sar or by the protonated amine base, leading to a regeneration of the amine base (Scheme 1).…”

“…It is important to note that initially the BnNH 2 should be protonated (BnNH Transformation of the Poc-Sar into the Sar-NCA, aided by the tertiary amine base, decreases the carboxylic acid content and causes a continuous shift of the primary ammonium-amine equilibrium (Scheme 1) toward BnNH 2 , which then can attack the Sar-NCA and initiate the polymerization. 26,28,29 Since the propagating chain end is a secondary amine, the polymerization rate should also be affected by the ammonium-amine equilibrium (actually, the rate should increase during polymerization). However, as long as the ammonium-amine exchange is faster than monomer addition, the resulting polysarcosine should still have a narrow molar mass distribution.…”

Synthesis of Poly‐γ‐S‐2‐methylbutyl‐l‐glutamate and Poly‐γ‐S‐2‐methylbutyl‐d‐glutamate and Their Use as Enantiodiscriminating Alignment Media in NMR Spectroscopy

“…In general, ROP of NCAs can be initiated with either a nucleophile or base . Additionally, organometallic catalysts and a wide range of metal‐free‐initiation approaches as the use of primary amine salts (e.g., primary amine hydrochlorides and primary amine fluoroborates), combined primary/secondary amine systems, combined thiourea/amine systems, N ‐trimethylsilyl amines (e.g., hexamethyldisilazane), or trimethylsilyl sulfides (e.g., phenyl trimethylsilyl sulfide) have been developed. Optimization of the reaction conditions (decreased temperature, removal of carbon dioxide by nitrogen flow or high‐vacuum techniques) further improves the control over the polymerization process.…”

Straightforward access to linear and cyclic polypeptides

“…Work toward this end has mainly been pioneered by Deming and co-workers [9][10][11] . The ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydrides (NCAs), initiated by amines or amine-derivatives (e.g., amine hydrochlorides 12,13 , amine trifluoroboranes 14 , and silazane derivatives 15,16 ), has emerged as a versatile method due to their advantages, including being a metal-free procedure and the absence of any toxic impurities. Intensive mechanistic studies have shown that two competitive mechanisms (the normal amine mechanism and the activated monomer mechanism) lead to undesirable side reactions, preventing the formation of welldefined polypeptides with controlled molecular weights (MWs) and low polydispersity index (Đ) 17,18 .…”