Carbobenzoxy-L-proline

A soln. of N-trifluoroacetylimidazole in dry tetrahydrofuran added at 0° to a soln. of N-carbohenzoxy-L-proline and p-nitrophenol in the same solvent, kept an additional hr. at 0°, then stirred 4 hrs. at room temp. N-carbobenzoxy-L-proline p-nitrophenyl ester. Y 78.5%. — In general, the use of 1-acylimidazoles seems less satisfactory then available alternatives, but may be useful in some specific instances. F. e. s. H. D. Law, Soc. 1965, 3897. 

A soln. of carbobenzoxy-L-proline p-nitrophenylester and tert-huiy leucinate in methylene chloride allowed to stand 48 hrs. at room temp. ferf-butyl carbobenzoxyprolyl-L-leucinate. Y 96%.—terf-Butyl esters are particularly useful in peptide synthesis, because the ester group can be removed by acid catalysis (s. Synth. Meth. 15, 12) and thus side reactions encountered in alkaline hydrolysis avoided. Other advantages arise from the stability of amino acid and peptide tert-butyl esters as free bases, particularly in allowing their storage. F. use, prepn., and hydrolysis of tert-butyl esters s. G. W. Anderson and F. M. Callahan, Am. Soc. 82, 3359 (1960) peptides from p-nitrophenyl esters s. a. J. Meienhofer and V. du Vigneaud, Am. Soc. 83, 142 (1961) B. Liberek, Chem. Ind. 1961,987. 

H-Carbobenzoxy-3-hydroxy-L-proline (purchased from either Mann Research Laboratories or Sigma Chemical Company) w as... 

Na and a trace of FeCls added under Og-free Ng to liq. NHg, methyltriphenyl-phosphonium bromide added with stirring when the blue color has disappeared, NH3 replaced by ether and tetrahydrofuran, the resulting suspension warmed 5 min. at 50°, a soln. of carbobenzoxy-4-oxo-L-proline in tetrahydrofuran added at room temp, with stirring during 10 min., refluxed several hrs., and the product isolated as the dicyclohexylammonium salt dicyclohexylammonium carbobenzoxy-4-methylene-L-prolinate. Y 84%. M. Bethell and G. W. Kenner, Soc. 1965, 3850. 

Plates DIOL F 254 HPTLC plates. Merck, Germany Eluent dichloromethane contg. 0.4 mM ethanolamine and 5 mM A/-carbobenzoxy glycyi-L-proline Visualization UV (280 or 300 nm)... 

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). 

Resolution The carbobenzoxy derivatives of DL-proline, DL-alanine, and dl-isoleucine have been resolved by fractional crystallization, in the lower alcohols or water, of the diastereoisomeric salts with L-tyrosine hydrazide. The yield is low in the case of DL-phenylalanine. 

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