Amino acid N-carboxyanhydrides

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

Kricheldorf HR (1987) a-Amino acid-N-carboxyanhydrides and related materials. Springer, New York... 

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... 

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... 

Knobler Y, Bittner S, Virov D, Frankel M (1969) Alpha-aminoacyl derivatives of aminoben-zoic acid and of amino-oxy-acids by reaction of their hydrochlorides with amino-acid N-carboxyanhydrides. J Chem Soc C 1821... 

Kramer JR, Deming TJ (2010) General method for purification of alpha-amino acid-N-carboxyanhydrides using flash chromatography. Biomacromolecules 11 3668-3672... 

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... 

Kricheldorf, H. R. a-Amino Acid-N-Carboxyanhydrides and Related Materials, Springer New York, 1987. 

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. 

R Hirschmann, H Schwam, RG Strachan, EF Schoenewaldt, H Barkemeyer, SM Miller, JB Conn, V Garsky, DF Veber, RG Denkewalter. The controlled synthesis of peptides in aqueous medium. The preparation and use of novel a-amino acid N-carboxyanhydrides. J Am Chem Soc 93, 2746, 1971. 

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... 

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. 

Deng and co-workers have also applied the cinchona derivatives to the kinetic resolution of protected a-amino acid N-carboxyanhydrides 51 [48]. A variety of alkyl and aryl-substituted amino acids may be prepared with high se-lectivities (krei=23-170, see Scheme 10). Hydrolysis of the starting material, in the presence of the product and catalyst, followed by extractive workup allows for recovery of ester, carboxylic acid, and catalyst. The catalyst may be recycled with little effect on selectivity (run 1, krei=114 run 2, krei=104). The reaction exhibits first-order dependence on methanol and catalyst and a kinetic isotope effect (A MeOH/ MeOD=l-3). The authors postulate that this is most consistent with a mechanism wherein rate-determining attack of alcohol is facilitated by (DHQD)2AQN acting as a general base. 5-Alkyl 1,3-dioxolanes 52 may also... 

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

NCA amino acid-N-carboxyanhydride N-carboxy-amino acid anhydride PNA peptide nucleic acid... 

S-Sulfenylamino acid N-carhoxyaidiydrides. The reagent reacts with an amino acid N-carboxyanhydride (NCA) to form o-nitrophenylsulfenyl (NFS) derivatives in high yield. I hus L-phenylafanine-NCA (1) reacts with the reagent in ethyl acetate or THF in the presence of triethylamine or 4-methylmorpholine to give NFS-L-phenyl-alanine-NCA (2) in 93% yield. The NFS-NCA amino acids are useful for peptide... 

W. D. Fuller, M. S. Verlander, and M. Goodman, A procedure for the facile synthesis of amino-acid N-carboxyanhydrides. Biopolymers 1976 15 1869-1871. 

Biron J-P, Pascal R. Amino acid N-carboxyanhydrides activated peptide monomers behaving as phosphate-activating agents in aqueous solution. J. Am. Chem. Soc. 2004 126 9198-9199. 

Figure 3 Plausible prebiotic pathways for the formation of a-amino acid N-carboxyanhydrides 21 from free amino acids, N-carbamoylamino acids 20, or activated a-amino acid derivatives 22.

Regarding the synthesis of AT -Fmoc-protected amino acid N-carboxyanhydrides (Leuchs anhydrides, amino acid-NCAs)t l as highly activated derivatives, see Section 3.4.4. 

Scheme 9 Reaction of a-Amino Acid iV-Carboxyanhydrides and Urethane-Protected a-Amino Acid N-Carboxyanhydrides with a Nucleophile ...

Abstract This article summarizes recent developments in the synthesis of polypeptides and hybrid peptide copolymers. Traditional methods used to polymerize -amino acid-N-carboxyanhydrides (NCAs) are described, and limitations in the utility of these systems for the preparation of polypeptides are discussed. Recently developed initiators and methods are also discussed that allow polypeptide synthesis with good control over chain length, chain length distribution, and chain-end functionality. The latter feature is particularly useful for the preparation of polypeptide hybrid copolymers. The methods and strategies for the preparation of such hybrid copolymers are described, as well as analysis of the synthetic scope of the different methods. Finally, issues relating to obtaining these highly functional copolymers in pure form are detailed. 

Rapid Synthetic Procedures. The most interesting development of the year v/as the skillful use of a-amino acid N-carboxyanhydrides in a rapid synthesis in aqueous medi mi32. This procedure is much faster than the Merrifield "solid phase" synthesis, vmdoubtedly more econoraical, and probably easier to adapt to larger scale syntheses. It appears that more byproducts are formed, but both methods require chroniatographic or more elaborate purification of the final products. 

There are several ways to prepare peptides, polypeptides, and artificial proteins carrying these aromatic amino acids as their constituents. Homopolypeptides can be prepared by the polymerization of amino acid N-carboxyanhydrides (NCAs) derived from the corresponding amino acids ( ). Sequential polypeptides of the form (ABC...W) are prepared by the polymerization of the corresponding oligopeptide active esters ABC...W-X. Small peptides of any sequence can be synthesized by a step-by-step procedure (5). Finally, cultivation of some bacteria in the presence of artificial amino acids will possibly incorporate them into the proteins produced by the bacteria. In the following, attention will be focused on homopolypeptides and sequential copolypeptides carrying one type of chromophore on a chain. 

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