Carbobenzoxy-L-phenylalanine

Pentachlorophenyl dichloroacetate added with cooling to a soln. of carbobenzoxy-L-phenylalanine and triethylamine in dimethylformamide, and allowed to stand 20 min. at room temp. pentadilorophenyl carbobenzoxy-L-phenylalanate. Y 87%. F. e., also with trichloroacetates, s. M. Fujino and C. Hatanaka, Chem. Pharm. Bull. 16, 929 (1968). 

A soln. of carbobenzoxy-L-phenylalanine in dry pyridine treated at room temp, with p-nitrophenyl trifluoroacetate, and the product isolated after 10 min. 

Carbobenzoxy-L-phenylalanine dissolved in ethyl acetate with addition of pyridine, treated with di(p-nitrophenyl) carbonate, refluxed 3hrs., L-proline methyl ester hydrochloride in chloroform and triethylamine added, allowed to stand overnight at room temp., then the volatiles removed by distillation in vacuo crude carbobenzoxy-L-phenylalanyl-L-proline methyl ester. Y 87%. F. e. s. T. Wieland et al., A. 655, 189 (1962) cf. P. G. Katsoyannis et al., Am. Soc. 85, 1679, 1681 (1963) also reactions with 2,4-dinitrophenyl esters s. R. Glatthard and M. Matter, Helv. 46, 795 (1963). 

Carbobenzoxy-L-phenylalanine N-hydroxyphthalimide ester and ethyl glycinate hydrochloride dissolved in a small amount of dimethylformamide, cooled to ca. —10°, 2 moles of triethylamine added with stirring, and the product isolated after 1 min. ethyl carbobenzoxy-L-phenylalanylglycinate. Y 96%.—N-Hy-droxyphthalimide liberated during the reaction can be easily removed. F. e. s. G. H. L. Nefkens, G. I. Tesser, and R. J. F. Nivard, R. 81, 683 (1962) with N-hydroxysuccinimide esters cf. G. W. Anderson, J. E. Zimmerman, and F. M. Callahan, Am. Soc. 85, 3039 (1963). 

A soln. of carbobenzoxy-L-phenylalanine in abs. tetrahydrofuran cooled to —15°, treated with diphenylketene, triethylamine, and, after 1 min., with ethyl glycinate, allowed to warm to room temp., and the product isolated after 2 to 3hrs. -> ethyl carbobenzoxy-L-phenylalanylglycinate. Y 60%.—Aminolysis occurs preferentially at the sterically hindered diphenylacetyl group of the intermediate mixed anhydride. The optical activity of the reactants is retained. F. e. s. G. Losse and E. Demuth, B. 94, 1762 (1961). 

N-Carbobenzoxy-S-benzyl-L-cysteinyl-L-tyrosyl-L-phenylalanine azide Ornipressin... 

N-Carbobenzoxy-L-glutaminyl-L-asparaginyl-S-benzyl-L-cysteinyl-azide N-Carbobenzoxy-S-benzyl-L-cysteinyl-L-tyrosyl-L-phenylalanine azide Sodium Ammonia... 

In (Section 8) we have considered kinetic phenomena encountered during the copolymerization of L- and D-enantiomorphs of a single type of NCA. Copolymerization of mixtures of NCAs of different a-amino acids to give random copolymers is readily realizable [2], one of the earliest examples reported being the synthesis of a DL-phenylalanine L-leucine copolymer by Woodward and Schramm [78]. However, there are few reports on the kinetics of random copolymerization. Shalitin and Katchalski [79] studied the copolymerization of the NCAs of 7-benzyl L-glutamate (A) and e,N-carbobenzoxy L-lysine (B) initiated by diethyl-amine in N,iV-dimethylformamide at 25°C and obtained the interesting result that the over-all rate of reaction (measured by the CO2 evolution) is equal to the sum of the rates of reaction of the individual monomers under similar conditions. The copolymerization is represented schematically in (60)... 

The following pairs of NCAs behaved similarly when copolymerized under the same conditions [79] L-phenylalanine + e,AT-carbo-benzoxy-L-lysine, L-phenylalanine + 7-benzyl-L-glutamate, glycine + e,A/ -carbobenzoxy-L-lysine, e,AT-carbobenzoxy-L-lysine + DL-alanine and 7-benzyl-L-glutamate + DL-alanine. On the other hand, copolymerization of 7-benzyl-L-glutamate and DL-alanine NCAs behaved in a different manner and showed retardation in the later stages. 

The first protease-catalyzed reaction in ILs was the Z-aspartame synthesis (Scheme 10.7) from carbobenzoxy-L-aspartate and L-phenylalanine methyl ester catalyzed by thermolysin in [BMIM] [PF ] [ 14]. Subtilisin is a serine protease responsible for the conversion of A -acyl amino acid ester to the corresponding amino acid derivatives. Zhao et al. [90] have used subtilisin in water with 15% [EtPy][CF3COO] as cosolvent to hydrolytically convert a series of A -acyl amino acid esters often with higher enantioselectivity than with organic cosolvent like acetonitrile (Scheme 10.8, Table 10.2). They specifically achieved l-serine and L-4-chlorophenylalanine with an enantiomeric access (ee) of-90% and -35% product yield which was not possible with acetonitrile as a cosolvent [90]. Another example is hydrolysis of A-unprotected amino acid ester in the presence of a cysteine protease known as papain. Liu et al. 

A soln. of carbobenzoxy-L-prolyl-L-phenylalanine, p-nitrobenzyl tosylate, and triethylamine refluxed 1 hr. in dry acetone carbobenzoxy-L-prolyl-L-phenyl-alanine p-nitrobenzyl ester. Y 86%.—No racemization occurs. F. e. s. D. Theo-doropoulos and J. Tsangaris, J. Org. Chem. 29, 2272 (1964). 

Peptides. N-Bromosuccinimide added slowly to a soln. of carbobenzoxy-L-leucine phenylhydrazide and pyridine in dichloromethane, after 20 min. washed with water, dried with anhydrous Na-sulfate, and the resulting soln. added slowly in the dark to a soln. of ethyl L-phenylalaninate hydrochloride... 

Triethylamine and N-chloromethylphthalimide added to a soln. of carbo-benzoxy-L-phenylalanine in dry ethyl acetate, allowed to stand overnight at 37°, then refluxed 15-30 min. phthalimidomethyl carbobenzoxy-L-phenyl-alaninate. Y 70-80%.—No racemization takes place and the esters can be cleaved under mild conditions. F. e. s. G. H. L. Nefkens, Nature 193, 974 (1962). 

Diphenyl phosphoryl azide in dimethylformamide followed by triethylamine added at or below 0° to a soln. of N-carbobenzoxy-L-leucyl-L-leucine and L-valyl-L-phenylalanine methyl ester hydrochloride in the same solvent, stirred several hrs. at the above temp, and overnight at room temp. -> product. Y 87%. - Practically no racemization occurred. F. e., also direct prepn. of urethans from carboxylic acids (cf. Synth. Meth. 17, 393) by a simplified Curtius degradation, s. T. Shioiri, K. Ninomiya, and S. Yamada, Am. Soc. 94, 6203 (1972) Tetrah. Let. 1973, 2343 synthesis of N-subst. carboxylic acid amides and peptides with diethyl phosphoryl cyanide s. Tetrah. Let. 1973, 1595 coupling reagents in peptide synthesis, review, s. Y. S. Klausner and M. Bodansky, Synthesis 1972, 453 review of peptide synthesis s. J. Meienhofer, Chem. Technol. 3, 242 (1973). 

Poly(L-phenylalanine-co-s-carbobenzoxy-L-lysine) see poly(s-carbobenzoxy-L-lysine-co-L-phenylalanine) 225-226... 

Cyclobis(N-methyl-L-phenylalanyl), 42B, 358 N-Acetyl L phenylalanyl-L-tyrosine, 39B, 365 Carbobenzoxy-L-leucyl-p-nitrophenyl ester, 40B, 462 6, L-Threonyl-L-phenylalanine-p-nitrobenzyl ester hydro-bromide, 34B, 274... 

GIA Giacommeti, G., Turolla, A., and Boni, R., Enthalpy of helix-coil transitions from heats of solution, n. Poly-eps-carbobenzoxy-L-lysine and copolymers with L-phenylalanine, Biopolymers, 9, 979, 1970. 

Kusano, M., Yasukawa, K., Inouye, K. (2010). S5mthesis of N-carbobenzoxy-l-aspartyl-1-phenylalanine methyl ester catalyzed by thermolysin variants with improved activity. Enzyme Microb. Technol., 46,320-325. 

L-Phenylalanine, N-carbobenzoxy Chymotrypsin Exchange Sprinson and Rittenberg (1951)... 

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