L-Aspartate

The outputs of L-phenylalanine (31) and of L-aspartate (30) have recently risen to supply the demand for the starting materials for the synthesis of 

This stereoselective synthesis of the required enantiomer from a simple achiral precursor such as an alkene would be a preferred route for any chiral product. Even if a racemisation, such as that which accompanies the synthesis of L-methionine and L-cysteine, is practical, there are likely to be fewer steps in a selective synthesis fi om a carefully chosen achiral compound. In this instance the manufacture is very efficient. It is catalysed either by whole E. coli cells or by an enzyme preparation extracted from them. In 

Although the natural penicillins, G (32) and V (33), are useful antibiotics in their own right, their development as major pharmaceutical products was limited until a convenient method for the exchange of their 6-amido side chain was discovered. The new side chains increase the antibiotic activity of the jS-lactam and improve their resistance to the bacterial jS-lactamases, which will hydrolyse the jS-lactam ring. These two effects create some very valuable commercial products whose annual sales exceed 10 . 

The enzyme derived from E. coli will hydrolyse penicillin G to 6-APA, and this quiddy became the basis of a manufacturing process. Some 10 years later a similar process for hydrolysis of penicillin V was developed, relying on an enzyme from a basidiomycete, Pleurotus oestratus. The reactions are usually performed at about pH 8, and the yield of recovered 6-APA is about 90%. 

A chemical process was subsequently developed in which PO5 was used to break the amide bond. Partly for patent reasons, and partly because of the process chemist s general familiarity with chemistry rather than with enzymology, this chemical route competed effectively with the enzymatic catalysis for a number of years. This was particularly true for the hydrolysis of penicillin V, where for some time a suitable enzyme was not available. However, virtually all of the 16,000 tonnes of penicillin which is now converted to 6-APA is subject to enzymatic hydrolysis. 

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The naturally occurring substance is L-aspartic acid. One of the acidic-amino acids obtained by the hydrolysis of proteins. 

There are numerous further appHcations for which maleic anhydride serves as a raw material. These appHcations prove the versatiHty of this molecule. The popular artificial sweetener aspartame [22839-47-0] is a dipeptide with one amino acid (l-aspartic acid [56-84-8]) which is produced from maleic anhydride as the starting material. Processes have been reported for production of poly(aspartic acid) [26063-13-8] (184—186) with appHcations for this biodegradable polymer aimed at detergent builders, water treatment, and poly(acryHc acid) [9003-01-4] replacement (184,187,188) (see Detergency). 

Manometric determiaation of L-lysiae, L-argioine, L-leuciae, L-ornithine, L-tyrosiae, L-histidine, L-glutamic acid, and L-aspartic acid has been reviewed (136). This method depends on the measurement of the carbon dioxide released by the T.-amino acid decarboxylase which is specific to each amino acid. 

Enzymatic Process. Chemically synthesized substrates can be converted to the corresponding amino acids by the catalytic action of an enzyme or the microbial cells as an enzyme source, t - Alanine production from L-aspartic acid, L-aspartic acid production from fumaric acid, L-cysteine production from DL-2-aminothiazoline-4-catboxyhc acid, D-phenylglycine (and D-/> -hydtoxyphenylglycine) production from DL-phenyUiydantoin (and DL-/)-hydroxyphenylhydantoin), and L-tryptophan production from indole and DL-serine have been in operation as commercial processes. Some of the other processes shown in Table 10 are at a technical level high enough to be useful for commercial production (24). Representative chemical reactions used ia the enzymatic process are shown ia Figure 6. 

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

L-aspartic acid fumaric acid + NH aspartase E. coii ... 

The existence of protein receptors in the tongues of mice and cows have been shown. Monosodium L-glutamate MSG [142-47-2] is utilized as a food flavor enhancer in various seasonings and processed foods. D-Glutamate is tasteless. L-Aspartic acid salt has a weaker taste of umami. Glycine and L-alanine are slightly sweet. The relationship between taste and amino acid stmcture has been discussed (222). 

Aspartame (L-aspartyl-L-phenylalanine methyl ester [22839-47-0]) is about 200 times sweeter than sucrose. The Acceptable Daily Intake (ADI) has been estabUshed by JECFA as 40 mg/kg/day. Stmcture-taste relationship of peptides has been reviewed (223). Demand for L-phenylalanine and L-aspartic acid as the raw materials for the synthesis of aspartame has been increasing, d-Alanine is one component of a sweetener "Ahtame" (224). 

Aspartame (1) is the primary nonnutritive sweetener used in carbonated soft drinks. It is approximately 200 times sweeter than sucrose. Aspartame is the methyl ester of a dipeptide of T.-phenylalanine and L-aspartic acid. 

L-asparaginase, which catalyzes the hydrolysis of L-asparagine to L-aspartate. 

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. 

It is a peptide containing 27 amino acid residues containing the amino acids L-histidine (His) L-aspartic acid (Asp) L-serine (Ser) glycine (Gly) L-threonine (Thr) L-phenyl-alanine (Phe) L-glutamic acid (Glu) L-glutamine [Glu(NHj)] L-leucine (Leu) L-arginine (Arg) L-alanine (Ala) and L-valinamide (Va -NHj). 

Labetalol HCI 4-Benzyloxyaniline HCI Hydroxytryptophan N-BenzyloxycarbonyI-L-aspartic acid-a-nitrophenyl,/3-benzyl diester Aspartame... 

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