Synthesis of poly(Nε‐phenoxycarbonyl‐l‐lysine) by polycondensation of activated urethane derivative and its application for selective modification of side chain with amines

Abstract

We report a methodology for the synthesis of Nε‐phenoxycarbonyl‐protected poly(l‐lysine) on the side chain by chain growth polycondensation of Nα,Nε‐bis(phenoxycarbonyl)‐l‐lysine proceeded through the selective elimination of phenol and CO2 from the Nα phenoxycarbonyl moiety at 50 °C in N,N‐dimethylacetamide in the presence of a primary amine used as an initiator. After optimization of reaction condition, the addition of acetic acid during polycondensation proved effective for the realization of the predicted molecular weight and narrow dispersity of the corresponding polypeptide by adjusting the feed ratio of monomer to the amine initiator because of the suppression of interchain coupling that occurs between the amino terminus of poly(l‐lysine) and the Nε‐phenoxycarbonyl group on the polymer side chains. Furthermore, taking advantage of the potentially reactive Nε‐phenoxycarbonyl moiety on the side chain, post‐polymerization modification was effectively achieved by the nucleophilic reaction of amine compounds including primary, secondary, and aromatic amines through the formation of urea linkage, providing a useful platform for synthesis of selective side chain functionalization of poly(l‐lysine) samples. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 2522–2530

Well‐defined, environment‐friendly synthesis of polypeptides based on phosgene‐free transformation of amino acids into urethane derivatives and their applications

“…When the monohydrochloride of L-lysine is treated with DPC in the presence of triethylamine, both the amino groups are transformed into O-phenylurethanes. 17 It is noteworthy that, in this case, for the conversion of L-lysine into the corresponding urethane derivative its transformation into its tetrabutylammonium salt is not necessary. The obtained urethane undergoes polymerization on addition of n-butylamine to produce the corresponding polypeptide (Scheme 24).…”

“…l ‐Lysine, which has two amino groups, is also an interesting starting material for generating a reactive polypeptide (Scheme ). When the monohydrochloride of l ‐lysine is treated with DPC in the presence of triethylamine, both the amino groups are transformed into O ‐phenylurethanes . It is noteworthy that, in this case, for the conversion of l ‐lysine into the corresponding urethane derivative its transformation into its tetrabutylammonium salt is not necessary.…”

Well-Defined Construction of Functional Macromolecular Architectures Based on Polymerization of Amino Acid Urethanes

“…No racemization of the amino acid chiral center is observed. This method enables the efficient conversion of several amino acids bearing alkyl [17], allyl [18], and indolyl [19] groups, as well as protecting hydroxyl [20,21], sulfur-containing [17,22,23], ester [16], amide [20,24], and urethane [25][26][27] groups. It is important to note that L-tryptophan is converted into the corresponding urethane 2f, which can be used for the synthesis of poly(L-tryptophan) [19].…”

“…Urethane 2m can be copolymerized with other amino acid-derived urethanes such as L-lysine-derived urethane 2r, resulting in the density control of the styrenic moieties distributed in the copolypeptides. Urethane 2q, which can be synthesized by treating monohydrochloride of L-lysine with DPC in the presence of triethylamine, undergoes polymerization upon the addition of butylamine (Scheme 18) [25]. In the cyclization of 2q to the corresponding NCA, only the urethane moiety at the α-position is used, whereas the urethane moiety at the ε-position remains intact.…”

“…As a result, the target polypeptide is synthesized in a controlled manner. The urethane moiety successfully incorporated into the side chain is used for the reactions with various amines (Scheme 19) [25]. The resulting poly(L-lysine) derivatives are functionalized with the residues originated from the amines that are tethered to the main chain via the urea linkage.…”