Aspartic acid, decarboxylation

It is clear that biological systems can manage the chemical reactivity of unstable species. For example, oxalo-acetate—a metabolic intermediate in terran metabolism that is a precursor of citric acid, malic acid, and the amino acid aspartic acid—decarboxylates readily, with a half-life measured in minutes at room temperature at neutral pH. The half-life for the decarboxylation of oxaloacetate drops to seconds at high temperatures in pure water. It is not clear how microorganisms that live at high temperatures manage the instability of oxaloacetate, which is a key intermediate in standard biochemistry for the formation of amino acids, such as aspartate, and asparagine. 

Aspartic acid decarboxylase cataly2es the decarboxylation of asparatic acid to yield P-alanine (10), a precursor for the biosynthesis of pantothenic acid (67). FiaaHy, (R)-pantothenic acid is obtaiaed by coupling P-alaniae (10) with (R)-pantoate (22) ia the presence of pantothenate synthetase ... 

A more general method for preparation ofa-amino acids is the amidotnalmatesynthesis, a straightforward extension of the malonic ester synthesis (Section 22.7). The reaction begins with conversion of diethyl acetamidomalonate into an eno-late ion by treatment with base, followed by S 2 alkylation with a primary alkyl halide. Hydrolysis of both the amide protecting group and the esters occurs when the alkylated product is warmed with aqueous acid, and decarboxylation then takes place to vield an a-amino acid. For example aspartic acid can be prepared from, ethyl bromoacetate, BrCh CCHEt ... 

In the published synthesis the ozonolysis is performed on the protected product (9) and aldehyde (10) isolated before oxidation, hydrolysis and decarboxylation give aspartic acid. 

D-Aspartic acid 16 Apoxycillin Antibacterial Decarboxylation Pseudomonas dacunhae Immobilized cells [10]... 

The first designed catalyst where there was some understanding of the relationship between structure and function was oxaldie 1, a 14-residue peptide that folds in solution to form helical bundles [11] (Fig. 12). Oxaldie 1 was designed to catalyze the decarboxylation of oxaloacetate, the a-keto acid of aspartic acid, via a mechanism where a primary amine reacts with the ketone carbonyl group to form a carbinolamine that is decarboxylated to form pyruvate. The reaction is piCj dependent and proceeds faster the lower the piC of the primary amine if the reaction is carried out at a pH that is lower than the piCj, of the reactive amine. The sequence contains five lysine residues that in the folded state form... 

Cultures of Streptomyces rimosus var paromomycinus characteristically develop UV absorption at 240 and 278 nm due to formation of malonomicin (22), a compound that shows antiprotozoal activity towards Trypanosoma congolense, the causative agent of sleping sickness in cattle [42]. Malonomicin contains an unique aminomalonic acid unit that, on brief heating in water, undergoes decarboxylation and results in a compound devoid of biological activity [43]. Hydrolysis of the compound yielded L-serine and racemic aspartic acid. The structure was elucidated by chemical and spectroscopic methods [43,44] and was confirmed by total synthesis [45]. 

Pyridoxal-5 -phosphate participates in many reactions with a-amino acids, including transaminations, a decarboxylations, racemizations, a,/3 eliminations, j8,y eliminations, aldolizations, and the (3 decarboxylation of aspartic acid. 

The perhydroxy radical formed on the y-carbon atom (Reactions 30 and 31) is a likely precursor of aspartic acid, which we have found in yields of G = 1.1 when PGA was irradiated in 0.1% solution in 02. Further oxidation and a decarboxylation step would be required to give aspartic acid. However, it is not yet known whether the aspartic acid is formed solely as a result of irradiation it may be formed from a labile precursor during acid hydrolysis of the polymer. Our results differ from those reported by Friedberg and Hayden, who found high yields of aspartic acid in PGA irradiated in the absence of 02 we found only traces of aspartic acid from solutions of PGA irradiated under N2 (Figure 3). Glycine formation was not affected by the presence of 02. 

The hydrolysis product is a substituted derivative of malonic acid and undergoes decarboxylation on being heated. The product of this decarboxylation is aspartic acid (in its protonated form under conditions of acid hydrolysis). 

L-Aspartic acid (12) is an industrially important, large volume, chiral compound. The primary use of aspartic acid in the fine chemical arena is in the production of aspartame, a high potency sweetener (Chapter 31). Other uses of L-aspartate include dietary supplements, pharmaceuticals, production of alanine (by decarboxylation), antibacterial agents, and lubricating compounds. There have been a number of reviews on L-aspartate production.53 56... 

Scheme 1.6.3. Biosynthesis of p-alanine 3 by decarboxylation of (S)-aspartic acid 4.

A third amino acid synthesis begins with diethyl a-bromomalonate. First the Br is replaced by a protected amino group using the Gabriel synthesis (see Section 10.6). Then the side chain of the amino acid is added by an alkylation reaction that resembles the malonic ester synthesis (see Section 20.4). Hydrolysis of the ester and amide bonds followed by decarboxylation of the diacid produces the amino acid. An example that shows the use of this method to prepare aspartic acid is shown in the following sequence ... 

Alanine and aspartic acid are produced commercially utilizing enzymes. In the case of alanine, the process of decarboxylation of aspartic acid by the aspartate decarboxylase from Pseudomonas dacunhae is commercialized. The annual world production of alanine is about 200 tons. Aspartic acid is produced commercially by condensing fumarate and ammonia using aspartase from Escherichia coli. This process has been made more convenient with an enzyme immobilization technique. Aspartic acid is used primarily as a raw material with phenylalanine to produce aspartame, a noncaloric sweetener. Production and sales of aspartame have increased rapidly since its introduction in 1981. Tyrosine, valine, leucine, isoleucine, serine, threonine, arginine, glutamine, proline, histidine, cit-rulline, L-dopa, homoserine, ornithine, cysteine, tryptophan, and phenylalanine also can be produced by enzymatic methods. 

Such interference falls into two classes competitive substrates and substances that either aaivate or inhibit the enzyme. With some enzymes, such as urease, the only substrate that reacts at reasonable rate is urease hence, the urease-coated electrode is specific for use (59, 165). Likewise, uricase acts almost specifically on uric acid (167), and aspartase on aspartic acid (8, 168). Others, such as penicillinase and amino oxidase, are less specific (63,169,170). Alcohol oxidase responds to methanol, ethanol, and allyl alcohol (171, 172). Hence, in using electrodes of these enzymes, the analyte must be separated if two or more are present (172). Assaying L-amino acids by using either the decarboxylative or the deaminating enzymes, each of which acts specifically on a different amino... 

The oxidative decarboxylation of aliphatic carboxylic acids is best achieved by treatment of the acid with LTA in benzene, in the presence of a catalytic amount of copper(II) acetate. The latter serves to trap the radical intermediate and so bring about elimination, possibly through a six-membered transition state. Primary carboxylic acids lead to terminal alkenes, indicating that carbocations are probably not involved. The reaction has been reviewed. The synthesis of an optically pure derivative of L-vinylglycine from L-aspartic acid (equation 14) is illustrative. The same transformation has also been effected with sodium persulfate and catalytic quantities of silver nitrate and copper(II) sulfate, and with the combination of iodosylbenzene diacetate and copper(II) acetate. ... 

Hexenyl radicals cyclize to cyclopentylmethyl radicals (see Volume 4, Chapter 4.2). Thus radical decarboxylation of 6-heptenoic acids, by whatever means, usually results in die formation of five-mem-v beied rings. Although this fact had been appreciated previously it is only recendy, widi the advent of the 0-acyl thiohydroxamates, that it has been exploited from a syndietic point of view. An example is provided by the synthesis of bicyclo[4.3.0]proline derivatives from aspartic acid carried out by the Barton group (equation 51). It will be noted that activation of die C—C double bond acting as a radical trap is not necessary in these intramolecular reactions. 

Related Reactions. The photochemistry (Patemo-Biichi reactions) of the achiral oxazoline (7) has been studied. The analogous urethane (8), which is chiral by attachment of an apocam-phanoyl group, shows an intriguing stereoselectivity pattern in its reaction with electrophiles. For another case of an oxidative decarboxylation as a key step in the application of the SRSC (selfregeneration of stereogenic centers) principle, see the preparation of the dihydropyrimidone (9) from aspartic acid. ... 

The second pathway is called the C4 cycle because COj is initially converted to the four-carbon dicarboxylic acids, malic or aspartic acids (Fig. 3.3). Phos-phoenolpyruvic acid (I) reacts with one molecule of CO2 to form oxaloacetic acid (II) in the mesophyll of the biomass, and then malic or aspartic acid (III) is formed. The Q acid is transported to the bundle sheath cells, where decarboxylation occurs to regenerate pyruvic acid (IV), which is returned to... 

This vitamin is synthe.sized by most green plants and microorganisms. The precursors are y-ketoisovaleric acid and /S-alanine. The latter originates from the decarboxylation of aspartic acid. y-KetoLsovalcric acid is converted to keto-pantoic acid by Ar.W" -methyIenetetrahydrofolic acid then, on reduction, pantoic acid is formed. Finally, pantoic acid and alanine react by amide formation to form pantothenic acid. 

The action of the lysine-rich polymers was rather selective for OAA, in that pyruvic, malic, malonic, a-ketoglutaric, glucuronic, oxalic, or aspartic acid were not measurably decarboxylated under conditions in which OAA was 90% decarboxylated. Acetoacetic acid was decarboxylated about - 6 as fast as OAA. This selectivity is not in conflict with other reports of decarboxylation of some of these substrates, because conditions of assay have varied rather widely. The rate of decarboxylation may be essentially related to the relative stability of the substrate in question. Two reactions catalyzed separately by different types of thermal polymers describe a sequence, namely OAA pyruvate-> acetate. This sequence can be considered in the context of the beginnings of metabolism (p. 408). 

---