Glutamic anhydrides

A-Phthalyl-L-glutamic anhydride was converted in four steps into an aldehyde which reacted with Cys to give a thiazolopyridine derivative after cyclization (Scheme 51) (85TL647). 

The synthetic potential of salt 19 was demonstrated by the synthesis of coprine 23, which was readily obtained from the hydrochloride by acylation with A -phthaloyl-L-glutamic anhydride in tetrahydrofuran in the presence of triethylamine, followed by removal of the blocking group with hydrazine at pH... 

Materials. Three samples of poly-7-benzyl-L-glutamate were studied. Polymer I was obtained by polymerizing 7-benzyl A-carboxy-L-glutamate anhydride by sodium methoxide in DMF and polymer II by a similar polymerization using n-hexylamine as initiator. Both were purified by reprecipitation. The molecular weights determined from the viscosity-molecular weight ratio of Doty et al. (4) were 67,000 for polymer I and 21,000 for polymer II. Polymer III was a commercial sample (Pilot Chemical Co.) of molecular weight 275,000. All solvents were purified by standard laboratory procedures. 

N-Phthaloyl-L-glutamic anhydride This derivative of L-glutamic anhydride can be prepared without racemization as illustrated. The product is useful for... 

Thionyl chloride added to a stirred soln. of L-glutamic acid in trifluoroacetic acid, after 30 min. ether added slowly until the precipitate no longer dissolves -> L-glutamic anhydride hydrochloride. Y 88%. F. e. s. J. Kollonitsch and A. Rosegay, Ghem. Ind. 1964, 1867. 

When 1,4-benzoquinone is used, a mixture of 4-hydroxyphenyloxy a- and P-aspartates (hydroquinone monoesters) is obtained. Complex mixtures are obtained by using 1,4-naphthoquinone. No functionalization was achieved in any case with nickelacycles derived from glutamic anhydrides, and only products from P-elimination were observed. 

In the third method benzyloxycarbonyl-L-glutamic anhydride is condensed with an amine, amino acid or amino acid ester with subsequent removal of the benzyloxycarbonyl group by hydrogenation. This method gives a mixture of the a- and y-isomers, which are easily separated by... 

Larsen, P. O., and H. S0rensen y-Glutamyl-phenylalanine and y-L-glutamyl-L-tyrosine from seeds of Aubrietia deltoidea DC. Acta Chem. Scand. 21, 2908 (1967). Le Quesne, W. J., and G. T. Young Amino acids and peptides. Part I. An examination of the use of carbobenzyloxy-L-glutamic anhydride in the synthesis of glutamyl-peptides. J. Chem. Soc. 1950, 1954. 

The synthesis of II is accomplished by two different methods. The first method (427) (diagram 3) involves the following steps. Cbzo-glutamic anhydride (b,) (pre-... 

A different method was utilized to prepare III (24) in order to avoid all possible doubt, resulting from the utilization of the Cbzo-glutamic anhydride, which reacts to give a mixture of isomers a and 7 (378,435). This method is based on the opening of the lactame bond of the pyrrolidone nucleus by treatment of 2-pyrrolidone-5-carboxylic acid and its amide with hydrogen chloride-saturated ethanol. 

N-Carbobenzoxy-L-glutamic anhydride hydrogenated with 10%-Pd-on-charcoal in dioxane under strictly anhydrous conditions until H -uptake ceases N-carboxy-L-glutamic anhydride (Y 83 ) treated with water whereupon violent COg-evolution takes place L-pyroglutamic acid (Y 79%). J. Kovacs, H. N. Kovacs, and R. Ballina, Am. Soc. S5, 1839 (1963). 

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