749. Reaction of N-carboxy-α-amino-acid anhydrides with hydrochlorides of hydroxylamine, O-alkylhydroxylamines, and amines; syntheses of amino-hydroxamic acids, amido-oxy-peptides, and α-amino-acid amides

Synthesis of Polypeptides by Ring-Opening Polymerization of α-Amino Acid N-Carboxyanhydrides

“…The modified amino acids were then converted to their corresponding NCA monomers to allow subsequent polymerization. CD analysis of the water-soluble polymer in deionized water at pH 7 revealed that it was in a disordered chain conformation [35,36]. The CD spectra of this polymer were also invariant with solution pH and buffer strength, consistent with this result.…”

“…Their strategy was to avoid formation of NCA anions, which cause significant chain termination after rearranging to isocyanocarboxylates [11,12], through use of primary amine hydrochloride salts as initiators. The reactivity of amine hydrochlorides with NCAs was first explored by the group of Knobler, who found that they could react hydrochlorides with NCAs to give single NCA addition products [35,36]. Use of the hydrochloride salt takes advantage of its diminished reactivity as a nucleophile compared to the parent amine, which effectively halts the reaction after a single NCA insertion by formation of an inert amine hydrochloride in the product.…”

“…To obtain controlled polymerization, and not just single NCA addition reactions, Schlaad's group increased the reaction temperature (from 40 to 80 C), which was known from Knobler's work to increase the equilibrium concentration of free amine, as well as increase the exchange rate between amine and amine hydrochloride [35,36]. Using primary amine hydrochloride end-capped polystyrene macroinitiators to polymerize Z-Lys NCA in DMF, Schlaad's group obtained polypeptide hybrid copolymers in 70-80% yield after 3 days at elevated temperature.…”

Arborescent micelles: Dendritic poly(γ‐benzyl l‐glutamate) cores grafted with hydrophilic chain segments

“…The Glu(OtBu) 2 ·HCl initiator was in the salt form and therefore behaved differently from a free amine initiator in the NCA polymerization, due to its much lower nucleophilicity. It was first pointed out by Knobler et al in 1964 that the primary amine salt is at equilibrium with its non‐protonated form, which is capable of NCA initiation through the normal amine mechanism (Scheme ) . The success of salt initiators for NCA polymerization led us to use Glu(OtBu) 2 ·HCl for the polymerization of Bz‐Glu‐NCA .…”

Poly(N,N‐dimethylacrylamide)‐block‐Poly(L‐lysine) Hybrid Block Copolymers: Synthesis and Aqueous Solution Characterization

“…In order to inhibit side reactions such as the activatedmonomer mechanism, [25] the PDMAMNH 2 macroiniator was converted to the corresponding ammonium salt (PDMAMNH þ 3 Cl À ) following a procedure reported in the literature. [17,30,[34][35][36][37] Subsequently, the PDMAMNH þ 3 Cl À chains were employed as the macroinitiator for the ROP of NCA-TFALL [6,10,12,13,25,29] resulting in the PDMAM x -block-PTFALL y diblock copolymers. The PDMAMNH 2 block length was kept constant in all cases, whereas the PTFALL length was varied systematically with the y values being equal to 10, 23, 42 and 98.…”