N-Carboxyanhydrides polymerization

Pickel DL, Politakos N, Avgeropoulos A, Messman JM (2009) A mechanistic study of alpha-(amino acid)-N-carboxyanhydride polymerization comparing initiation and termination events in high-vacuum and traditional polymerization techniques. Macromolecules 42 7781-7788... 

In a recent and presently sole example, peptoids have also been synthesized using N-carboxyanhydride polymerization. Cyclic peptoid polymers were made using... 

Grafting of Poly(y-Benzyl-L-Giutamate) to the Inner Walls of Alumina by N-Carboxyanhydride Polymerization... 

Deming TJ (2000) Living polymerization of alpha-amino acid-N-carboxyanhydrides. J Polym Sci Polym Chem 38 3011-3018... 

Vayaboury W, Giani O, Cottet FI, Bonaric S, Schue F (2008) Mechanistic study of alpha-amino acid N-carboxyanhydride (NCA) polymerization by capillary electrophoresis. Macromol Chem Phys 209 1628-1637... 

Peggion E, Cosani A, Mattucci AM, Scoffone E (1964) Polymerization of gamma-ethyl-L-glutamate-N-carboxyanhydride initiated by Di-N-butyl and Di-isopropyl amine. Biopolymers 2 69-78... 

Xiao CS, Zhao CW, He P, Tang ZH, Chen XS, Jing XB (2010) Facile synthesis of glycopo-lypeptides by combination of ring-opening polymerization of an alkyne-substituted N-carboxyanhydride and click glycosylation . Macromol Rapid Commun 31 991-997... 

Kramer JR, Deming TJ (2010) Glycopolypeptides via living polymerization of glycosylated-1-lysine N-carboxyanhydrides. J Am Chem Soc 132 15068-15071... 

Wang J, Gibson MI, Barbey R, Xiao SJ, Klok HA (2009) Nonfouling polypeptide brushes via surface-initiated polymerization of N-epsilon-oligo(ethylene glycol)succinate-L-lysine N-carboxyanhydride. Macromol Rapid Commun 30 845-850... 

Mori H, Iwata M, Ito S, Endo T (2007) Ring-opening polymerization of gamma-benzyl-L-glutamate-N-carboxyanhydride in ionic liquids. Polymer 48 5867-5877... 

In order to account for the nonvolatility, infusibility, and limited solubility, Leuchs postulated polymerization of the ground type cyclic compound, as indicated by the subscript x in his formula given above. It is now well established that linear polypeptides are produced on decarboxylation of the N-carboxyanhydrides of a-amino acids, and under favorable conditions the chain length may be fairly large. Leuchs favored the view that strained rings, i.e., those of other than five or six... 

The free amino group of the amino ester may then react analogously with another molecule of the monomer, etc. The kinetics of the polymerization are in harmony with a mechanism of this sort. The final polypeptide may contain up to 300 or more structural units. While the polymerization of N-carboxyanhydrides is closely analogous to the addition polymerizations of ethylene oxide and of other cyclic substances, definition unfortunately classifies it as a condensation polymerization inasmuch as carbon dioxide is eliminated in the process. 

The difficulties of devising a basis for conveniently classifying various polymerizations in an appropriate manner have been discussed earlier in this chapter and several borderline examples which offer particular difficulty have been mentioned. One of these, the polymerization of the N-carboxyanhydrides, falls within the definition of a condensation polymerization, proceeds by a mechanism resembling a vinyl addition polymerization, and yields a product which possesses the structure of a typical condensation polymer. Definitions have been... 

Other cyclic compounds such as the N-carboxyanhydrides of a-amino acids,and lactams may be polymerized similarly with regeneration of an amino group at each step. According to the mechanism postulated, the number of polymer molecules formed should equal the number of initiator molecules (e.g., ROH) introduced, and the average number of monomers per polymer molecule should equal the ratio of monomer consumed to initiator. 

Low molecular weight poly(/3-peptide)s may be synthesized in an analogous manner via the ROP of /3-amino acid-N-carboxyanhydrides.9 Longer chain materials may be prepared by the ROP of /3-lactams (Scheme 28). This polymerization is initiated by a range of metal amides, of which Sc[N(TMS)2]3 offers particularly high levels of control.997... 

K. Aoi, K. Tsutsumiuchi, A. Yamamoto, and M. Okada, Globular carbohydrate macromolecule sugar balls 3. Radial-growth polymerization of sugar-substituted x-amino acid N-carboxyanhydrides (glyco-NCAs) with a dendritic initiator, Tetrahedron, 53 (1997) 15415-15427. 

The results of a comprehensive 13 C CP/MAS NMR study of the structure of solid polypeptides, prepared by polymerization of amino acid N-carboxyanhydrides under various conditions, have been reported105,107. In the case of poly(L-alanine) it was found that... 

A-Carboxy-a-amino acid anhydrides, also referred to as 4-substituted oxazolidine-2,5-diones, Leuchs s anhydrides, or N-carboxyanhydrides (NCA), are polymerized by bases and transition metal complexes. Polymerization proceeds with simultaneous decarboxylation to produce a polyamide... 

Kricheldorf, H. R., Anionic Ring-Opening Polymerization of N-Carboxyanhydrides, Chap. 36 in Comprehensive Polymer Science, Vol. 3, G. C. Eastmond, A. Ledwith, S. Russo, and P. Sigwalt, eds., Pergamon Press, London, 1989. 

Plasson, R., Biron, J. P, Cottet, H., Commeyras, A., and Taillades, J. (2002). Kinetic study of the polymerization of alpha-amino acid N-carboxyanhydrides in aqueous solution using capillary electrophoresis. J. Chromatogr. A, 952, 239-48. 

Ab A) measured by CO evolution method as a function of time for an Afl 400 sodium methoxide initiated polymerization of y-benzyl-L glutamate-N-carboxyanhydride... 

Fig. 18. The polymerization constants kp, for sodium methoxide initiated polymerizations of y-benzyl-i-.glutamate-N-carboxyanhydride in dioxane solution (4 g/100 ml) as a function of mole per cent. D-anhydride isomer X, polymers made with m.-NCA and optically active NCA o, polymers made with mixtures of pure o- and pure t-NCA. [Reprinted from paper by Idelson and Blovi J. Am. Chem. Soc. 80, 2387 (1958)...

Ring-opening Polymerization of a -Amino Acid N-Carboxyanhydrides... 

The possibilities of amino acid thioesters in peptide synthesis have been demonstrated very early as well as the effect of carbon dioxide supporting the involvement of N-carboxyanhydrides in the hydrolysis and polymerization pathways [127,176,177]. Aminothioacids can also be converted into NCAs [152,178,179] but they can, in addition, be activated by oxidation into disulfides which are much more reactive [151]. 

The N-Carboxy-Amino Acid Anhydride Method. Since the isopeptide bond of e-methionyllysine was hydrolyzed readily by intestinal aminopeptidase and the released amino acid was biologically available, we decided to further increase the amount of covalently attached methionine through a polymerization reaction. The most suitable amino acid derivative for this approach is the N-carboxyanhydride or Leuchs anhydride. 

Synthesis and Polymerization of Leuchs Anhydrides. The N-carboxy-a-amino acid anhydrides, referred to as Leuchs anhydrides or as NCAs, are synthesized either from N-alkoxycarbonyl derivatives of a-amino acids or from free amino acids. Cyclization of the amino acid derivative by SOCl2 or similar reagents was described first by Leuchs in 1906, but direct synthesis involves treating the a-amino acid or its hydrochloride with phosgene as shown in Figure 4. This method, commonly termed the Fuchs-Farthing method, is the one that is used most frequently since the N-carboxyanhydride may be freed easily from the carbamyl chloride, isocyanate derivative, and hydrogen chloride by crystallization. 

N-Carboxyanhydride of a-amino add is polymerized by the nucleophile-containing polymers such as poly(N-vinyl-2-ethylimidazole), poly(N-vinyl-2-ethylimidazole-co-acrylamide) and poly(N-vinyl-2-ethylimidazole-co-N-vinylpyrrolidone) (102, 103). The rate of polymerization increases with the order of pyrrolidone, amide and imidazole moieties. The order corresponds to the magnitude of the bond formation which is observed in 1R measurement. The rate also increases with the content of pyrrolidone moiety. The rate in N, N -dimethylformamide solution which is unfavorable to the hydrogen bond formation is lower than that in acetophenone. These results show that the hydrogen bond formation is notable as the binding. 

---