1522 [CONTRIDU~IOXFROM
THE L)EPARTMEST OR
BIOCHEMISTRY, LTXIVERSITV
OF
CALIPORNIA, BEKKELEl’]
On the Preparation and Froperties of Some Amino Acid Amides1 BY ROBERT WARNER CHAMBERS~ AND FREDERICK H. CARPENTER RECEIVED SEPTEMBER 21, 1954 The preparation arid properties of the amides of a number of the conimonly occurring amino acids have been stutlieti. Iiicluded are syntheses of DL-isoasparagine and L-isoglutamine from the p-nitrobenzyloxycarbonvl derivatives of the corresponding amino acids and the preparation of 1.-isoglutaniine from diethyl 1,-glutamate hydrochloride. The apparriit (lissociation constants of the or-amino groups of the ainino acid amides as well 3 s the paper chromatographic behavior of the amides is reported.
In connection with studies conducted in this Laboratory on the ainmonolysis of peptidcs and protein^,^ it was necessary to prepare the amides of most of the commonly occurring amino acids for use as reference compounds in the identification of the ammonolysis products of peptides by t!ie technique of paper Chromatography. 2Wiough most of the ainino acid amides have been preparect p r e ~ i o u s l y ,it~ seemed desirable, in view of the increasing importance of the ainino acid amides in naturally occurring products,5to record the inforrnation we have obtained on various methods of p r e p ration and on the properties of these compounds. Eleven of these amides (see Table 111) were prepared in the present study as the DL-derivatives through ammonolysis of the corresponding methyl or ethyl esters of the ainino acids by procedures similar to those of Fischer and K o e n i g ~ . ~These ” amides were isolated in the present instance as their acetate salts, which, for the main part, have not been previously described in the literature. The preparation of isoglutaniine and isoasparagine presented special problems because of the presence of two carboxyl groups in the parent amino acids. Many of the methods which have been described for the preparation of the monoamides, as well as a- and &peptides, of aspartic acid have involved the use of a suitably blocked aspartic anhydride derivative (I, n = 1).6 In order to use this type of intermediate, there must he a preferential openinq of the anhydride ring in favor of the desired product. There is considerable evidence to indicate that the direction of the ring opcning depends on both the nature of the blocking group and the reaction conditions.’ In the synthesis of isoasparagine described here, the p nitrobenzyloxycarbonyl (PSBC) groupS was used as the means of blocking the amino group of the aspartic acid. (1) This wurk was wpported in part h y grants from Eli I i l l y nnd Cornpmy and the iYatioiial Institute for Arthritis and Metabolic
Diseases. (‘2) Part of this w i n k was p e r i o n l i d during the tenure f , f a du PonL Postgraduate Fellowshil~. (3) K TI’. Chambers and F. H Carpenter, Trim J O U R N A L , 77, 1527 (19551, (4) (a) E . Fischer and E. Kbenigs, Der., 87, 4585 (1904), (1.1 P. S . Yarig and hl. M . Rising, T m s J O U R N A L , 53, 3183 (1931). (5) V. du Vigneaud, C. Ressler, J. M. Swan, C. W. Roberts and P. G . Katsoyannis, ibid., 76, 3115 (1954); V. d u Vigneaud, H. C. LawIeC and E. A. Popenoe, $ b i d . , 76, 1880 (1R53). ((i)J . S.Fruton, Advnizces Protein Chem., 5 , 1 (1949). (7) ( a ) R l . Bergmnnn and I,. Zervas, Ber., 6 5 , 1192 (1932); F.E. I c i n g and D . A. A Kidd, J. C h w . So
