P- -L-aspartate

Scheme 6 Chemical structure of poly(p-L-aspartate)s with various contents of para- (X) and meta-phenylazobenzyl (XI) units in the side chains.

Figure 1 Chemical structures of comblike poly(y-alkyl-a,L-glutamate)s (PyAG-n), poly(P-alkyl-a,L-aspartate)s (PpAA-n), and poly(a-alkyl-P,L-aspartate)s (PaAA-n). n indicates the number of carbons in the polymethylene sidechain and the carbonyl position relative to the nitrogen atom is indicated by Greek letters.

Figure 2 (a) The 18/5 right-handed cx-helix typical of poly(a,L-peptide)s. (b) The 13/4 right-handed pseudo-a-helix observed in poly(a-alkyl-P,L-aspartate)s. In both helices the hydrogen bond scheme is set between every third amide group but counted at opposite directions with respect to the directionahty of the mainchain. The larger spheres represent the sidechains and hydrogen bonds are indicated as dotted lines. 

L-alanine L-aspartic acid Asp artic- P - decarb oxylase Pseud. dacunhae tQ 192... 

N-Benzyloxycarbonyl-L-aspartic acid-a-p-nitrophenyl, /3-benzyl Diester Hydrogen... 

A solution of 88.5 parts of L-phenylalanine methyl ester hydrochloride in 100 parts of water is neutralized by the addition of dilute aqueous potassium bicarbonate, then is extracted with approximately 900 parts of ethyl acetate. The resulting organic solution is washed with water and dried over anhydrous magnesium sulfate. To that solution is then added 200 parts of N-benzyloxycarbonyl-L-aspartic acid-a-p-nitrophenyl, -benzyl diester, and that reaction mixture is kept at room temperature for about 24 hours, then at approximately 65°C for about 24 hours. The reaction mixture is cooled to room temperature, diluted with approximately 390 parts of cyclohexane, then cooled to approximately -18°C in order to complete crystallization. The resulting crystalline product is isolated by filtration and dried to afford -benzyl N-benzyloxycarbonvI-L-aspartyl-L-phenylalanine methyl ester, melting at about 118.5°-119.5°C. 

The best results were obtained with L-aspartic add as the amino donor for P. denitrificam and phenylpyruvic add as the amino acceptor. With L-aspartic add, conversion of phenylpyruvic add exceeded 90%. This may be attributed to absence of feedback inhibition of the reaction due to metabolism of file reaction product, oxaloacetic add. When using glutamic acid the conversion of phenylpyruvic add did not exceed 60%. 

THE USE OF POLYSTYRYLSULFONYL CHLORIDE RESIN AS A SOLID SUPPORTED CONDENSATION REAGENT FOR THE FORMATION OF ESTERS SYNTHESIS OF N-[(9-FLUORENYLMETHOXY)CARBONYL]-L-ASPARTIC ACID a tert-BUTYL ESTER, P (2-ETHYL[(lE)-(4-NITROPHENYL)AZO] PHENYL]AMINO]ETHYL ESTER... 

Fig. 2.2 Most favored helical structures proposed for two crystal forms of poly(a-n-butyl-/ -L-aspartate) (7, R=Bu) [28]. (A) Model of a (P)-3.25i4-helix. (B) Model of a (P)-4is-helix...

N-[N-(benzyloxycarbonyl)-L-aspart-l-oyl-(L-alanyl-L-threonine p-nitrobenzyl ester)-4-oyl]-... 

N-[N-(benzyloxycarbonyl)-L-aspart-l-oyl-(L-alanyl-L-threonyl-L-leucyl-L-alanine p-nitrobenzyl ester)-4-oyl]-N-[N-(benzyloxycarbonyl)-L-aspart-l-oyl-(L-alanyl-L-threonyl-L-leucyl-L-alanyl-L-serine p-nitrobenzyl ester)-4-oyl]-N-[N-(benzyloxycarbonyl)-L-aspart-1 -oyl-(glycine ethyl ester)-4-oyl -N-[N-(benzyloxycarbonyl)-L-aspart-l-oyl-(glycyl-L-serine methyl ester)-4-oyl]-... 

N-[l-ethyl N-(benzyloxycarbonyl)-L-aspart-4-oyl]-N-[l-ethyl N-(benzyloxycarbonyl)glycyl-L-aspart-4-oyl]-N-[ 1 -ethyl N-(trifluoroacetyl)-L-aspart-4-oyl]-N-[ 1 -p-nitrobenzyl N-(benzyloxycarbonyl)-L-seryl-L-aspart-4-oyl]-N-[2-N-(L-tyrosyl)-L-aspart-4-oyl)-2-acetamido-2-deoxy-N-(N-acetyl-L-aspart-4-oyl)-... 

Kataoka K, Matsumoto T, Yokoyama M et al (2000) Doxorubicin-loaded poly(ethylene glycol)-poly(P-benzyl-L-aspartate) copolymer micelles their pharmaceutical characteristics and biological significance. J Control Release 64 143-153... 

Cyclocondensation processes of p-dicarbonyl derivatives or their analogues are still widely employed for the synthesis of new isoxazoles. Non-proteinogenic heterocyclic substituted ct-amino acids have been synthesised using the alkynyl ketone functionality as a versatile building block ynone 2, derived from protected L-aspartic acid 1, reacted with hydroxylamine hydrochloride affording the isoxazole 3 with enantiomeric purity greater than 98% ee <00 JCS(P 1 )2311 >. 

ACTase catalyzes the transfer of a carbamoyl residue from carbamoyl phosphate to the amino group of L-aspartate. The N-carbamoyl L-aspartate formed in this way already contains all of the atoms of the later pyrimidine ring (see p. 188). The ACTase of the bacterium Escherichia coli is inhibited by cytidine triphosphate (CTP), an end product of the anabolic metabolism of pyrimidines, and is activated by the precursor ATP. 

Aminotransferases are useful enzymes for the synthesis and manipulation of amino acids. Young et al. investigated the ability of PLP-dependent aminotransferases to catalyze 3-subshtuhon of L- and D-P-chloroalanine 51 using P-mercap-toethanol (Scheme 2.22). L-Aspartate aminotransferase and D-aminotransferase catalyzed the substitution of l-51 and d-51, respechvely, to 52 with retention of stereochemistry [24]. 

W13. Wolf, P. L., William, D., Coplon, N., and Coulson, A. S., Low aspartate transaminase activity in serum of patients undergoing chronic hemodialysis. Clin. Chem. 18, 567-568 (1972). 

Alternatively, oxazolones have been used as reagents to activate and to couple N-protected dicarboxylic amino acids wherein the carboxylate moiety acts as the nucleophile. For example, 2,4-dimethyl-5(4//)-oxazolone 255 reacts with N-benzyloxycarbonyl-L-aspartic acid to give a mixture of the anhydrides 256 and 257. Subsequent reaction of 256 and 257 with phenylalanine methyl ester hydrochloride and A-methylmorpholine produces a mixture of the a-isomer 258 and p-isomer 259 of Al-benzyloxycarbonyl-aspartylphenylalanine methyl ester (Scheme 7.83). °... 

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