A-Amino acid-N-carboxyanhydrides

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

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

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. 

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... 

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.

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

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. 

Pumera, M., Flegel, M., LepSa, L., and Jelfnek, I., Chiral analysis of biogenic DL-amino acids deriva-tized by urethane-protected a-amino acid N-carboxyanhydride using capillary zone electrophoresis and micellar electrokinetic chromatography, Electrophoresis, 23, 2449, 2002. 

UNCA Urethane-protected a-amino acid N-carboxyanhydride Z Benzyloxycarbonyl... 

Scheme 5.10 Anionic ring-opening polymerization of a-amino acid N-carboxyanhydride (NCA).

H. R. Kricheldorf, Polypeptides and 100 years of chemistry of a-amino acid N-carboxyanhydrides, Angew. Chem. Int. Edit, 45, 5752-5784 (2006). 

Abraham, S., Ha, C.-S., and Kim, I. (2006) Self-assembly of star-shaped polystyrene-WocA -polypeptide copolymers synthesized by the combination of atom transfer radical polymerization and ring-opening living polymerization of a-amino acid-N-carboxyanhydrides. Journal of Polymer Science Part A Polymer Chemistry,... 

Hadjichristidis, N., latrou, H., Pitsikalis, M. etal (2009) Synthesis of well-defined polypeptide-based materials via the ring-opening polymerization of a-amino acid N-carboxyanhydrides. Chemical Reviews, 109,5528-5578. 

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

Synthetic peptide-based polymers are not new materials homopolymers of polypeptides have been available for many decades, yet have only seen limited use in materials applications. However, new methods in chemical synthesis have made possible the preparation of increasingly complex polypeptide sequences of controlled molecular weight that display properties far superior to ill-defined homopolypeptides. Examination of the different methods for polypeptide synthesis reveals the limitations of these techniques for preparation of well-defined copolymers. Conventional solid-phase peptide synthesis is neither useful nor practical for direct preparation of large polypeptides (> 100 residues) due to unavoidable deletions and truncations that result from incomplete deprotection and coupling steps. The most economical and expedient process for synthesis of long polypeptide chains is the polymerization of a-amino acid N-carboxyanhydrides (NCAs)... 

The oldest example of a CCP in a laboratory are polymerizations of a-amino acid N-carboxyanhydrides (NCAs, 2,5-dioxo-oxazolidines, see Formula 16.2). Synthesis and polymerization of these amino acid derivatives were first described by Leuchs and coworkers in the years 1906-1908 [3-5]. The existence of long covalent polymer chains was not accepted by the scientific community at that time, and poly(a-amino acid)s which are insoluble in almost all organic solvents were difficult to characterize. Therefore, Leuchs abandoned this working field after three... 

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