2- -L-cysteine

Due to its extraordinary reactivity L-cysteine plays not only a crucial role for the cell s metabolism but it has gained importance in several fields of humans daily lives as well. 

Currently the world market of L-cysteine represents approximately 5,000 mtoa , approximately 55 Mio US sales and an annual growth rate of 4%, whereby its main fields of application are the pharmaceutical, food and cosmetic industries. About 30% of the annual L-cysteine requirement is converted into the derivatives N-acetylcysteine and S-carboxymethylcysteine 

1 Extraction from Natural Sources. Today, L-cysteine is one of the 

Another process makes use of the ability of some bacteria belonging to the genus Pseudomonas to convert DL-2-amino-thiazoline-4-carboxylic acid (DL-ATC) into L-cysteine. DL-ATC is synthesized chemically from 2-chloroacrylic acid and thiourea. Formation of L-cysteine from DL-ATC is a three-step process catalyzed by different enzymes inside the cells 1) racemization of DL-ATC to L-ATC by ATC racemase, 2) formation of N-carbamoyl-L-cysteine (L-NCC) from L-ATC by L-ATC hydrolase and 3) hydrolysis of L-NCC to L-cysteine, NH3 and CO2 by L-NCC-amino-hydrolase. 

Another benefit of this new process is the environmental sustainability since in contrast to the extraction process only 1 kg of hydrochloric acid is needed to receive 1 kg of L-cysteine, which corresponds to an acid reduction of more than 96%. This issue was honoured by the Federation of German Industries (BDI) in June 2008 when Wacker won the environmental prize in the Environmentally Compatible Technology category. 

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Chlorine Benzoyl peroxide L-Ascorbic acid L-Cysteine... 

The deterruination of amino acids in proteins requires pretreatment by either acid or alkaline hydrolysis. However, L-tryptophan is decomposed by acid, and the racemi2ation of several amino acids takes place during alkaline hydrolysis. Moreover, it is very difficult to confirm the presence of cysteine in either case. The use of methanesulfonic acid (18) and mercaptoethanesulfonic acid (19) as the protein hydroly2ing reagent to prevent decomposition of L-tryptophan and L-cysteine is recommended. En2ymatic hydrolysis of proteins has been studied (20). 

Refs. 21, 22, 155. Abbreviations AHV, a-amino-(3-hydroxyvaleric acid Horn, L-homoserine AEG, (3 -(2-aminoethyl)-L-cysteine ppc, phosphoenolpymvate carboxylase the strain improvement largely depends on the transduction technology sensitive resistant —, auxotroph or deficient , leaky auxotroph +, prototrophic revertant. Table 7. Amino Acid Production from Hydrocarbons ... 

Abbreviations Horn, homoserine AEG, 3 -(2-aminoethyl)-L-cysteine resistant —, auxotroph. ... 

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-cysteine (derivatives) /5-chloro-DL-alanine + Na2S Cys desulfhydrase Enterobactor cloacae 193... 

L-cysteine DL- 2- amino thia2 oline- 4- c arb 0 xyUc hydrolase + racemase Pseud, thia olinophilum ... 

L-cystathionine L-homoserine + L-cysteine cystathionine-y- synthase Streptomyces phaeochromogenes ... 

Original Synthesis. The first attempted synthesis of i7-biotin in 1945 afforded racemic biotin (Fig. I). In this synthetic pathway, L-cysteine [52-90-4] (2) was converted to the methyl ester [5472-74-2] (3). An intramolecular Dieckmaim condensation, during which stereochemical integrity was lost, was followed by decarboxylation to afford the thiophanone [57752-72-4] (4). Aldol condensation of the thiophanone with the aldehyde ester [6026-86-4]... 

Several mucolytics reduce the viscosity of mucus by cleaving the disulfide bonds that maintain the gel stmcture. AJ-Acet l-L-cysteine [616-91 -1] (19), introduced in 1963, and mesna [19677-45-5] (20), developed in Europe in the early 1970s (20,21), are effective compounds in this class. Whereas most mucolytics must be adrninistered by aerosol, carbocysteine [638-23-6] (21), which contains a derivatized sulfhydryl group, has shown activity by the oral route (22,23). However, carbocysteine does not reduce mucus viscosity, as does acetylcysteine, but appears to have a direct action on mucus glycoprotein production (24). 

Woodward s total synthesis of cephalosporin C begins with L-cysteine (48) which establishes the chiral center at C-7. The cis geometry at C-6,7 is achieved in intermediate (49) which is cyclized to (50) by treatment with triethylaluminum. The dihydrothiazine ring is constructed by Michael addition to the condensation product of trichloroethyl glyoxylate... 

Cystamine dihydrochloride, S,5-(L,L)-Cystathionine, Cysteamine, Cysteamine hydrochloride, ( )-Cysteic acid, S-Cysteic acid (H2O), L-Cysteine hydrochloride (H2O), ( )-Cysteine hydrochloride and L-Cystine, Cytidine, see entries in Chapter 6. 

L-Tyrosine [60-18-4] M 181.2, m 290-295 (dec), [aj -10.0 (5M HCl), pK 2.18 (CO2H), pK2 9.21 (OH), pK 3 10.47 (NH2). Likely impurities are L-cysteine and the ammonium salt. Dissolved in dilute ammonia, then crystd by adding dilute acetic acid to pH 5. Also crystd from water or EtOH/water, and dried at room temperature under vacuum over P2O5. 

Polypeptides. These are a string of a-amino acids usually with the natural 5(L) [L-cysteine is an exception and has the R absolute configuration] or sometimes "unnatural" 7f(D) configuration at the a-carbon atom. They generally have less than -100 amino acid residues. They can be naturally occurring or, because of their small size, can be synthesised chemically from the desired amino acids. Their properties can be very similar to those of small proteins. Many are commercially available, can be custom made commercially or locally with a peptide synthesiser. They are purified by HPLC and can be used without further purification. Their purity can be checked as described under proteins. 

Displacement of the sulfhydryl group in primary thiols, like L cysteine and 2-diethylaminoethanethiol, requires elemental fluorine, the most active oxidant Elemental sulfur is the major by-product in those reactions [7] (equation 2)... 

Reactions between A -(l-chloroalkyl)pyridinium chlorides 33 and amino acids in organic solvents have a low synthetic value because of the low solubility of the amine partner. A special protocol has been designed and tested in order to circumvent this drawback. Soon after the preparation of the salt, an aqueous solution of the amino acid was introduced in the reaction medium and the two-phase system obtained was heated under reflux for several hours. However, this was not too successful because sulfur dioxide, evolved during the preparation of the salt, was converted into sulfite that acted as an 5-nucleophile. As a result, A -(l-sulfonatoalkyl)pyridinium betaines such as 53 were obtained (Section IV,B,3) (97BSB383). To avoid the formation of such betaines, the salts 33 were isolated and reacted with an aqueous solution of L-cysteine (80) to afford thiazolidine-4-carboxylic acids hydrochlorides 81 (60-80% yields). 

Therapeutic Function Expectorant Chemical Name N-acetyl-L-cysteine Common Name —... 

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