Of L-cysteine

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). 

To a suspension of 35.2 grams (0.2 mol) of L-cysteine hydrochloride monohydrate stirred in a reaction vessel containing 87 ml of 91% aqueous tetrahydrofuran under a nitrogen... 

Several elegant synthetic strategies have been devised for biotin (1) this chapter describes one of the total syntheses developed at Hoffmann-La Roche. This insightful synthesis employs a derivative of L-cysteine, a readily available member of the chiral pool,2 as the starting material, and showcases the powerful intramolecular nitrone-olefin [3+2] cycloaddition reaction. 

The elegant, enantiospecific synthesis of biotin (1) by Hoffmann-La Roche1 is based on a strategy that takes advantage of the powerful intramolecular nitrone-olefin cycloaddition reaction. Our analysis begins with model studies in which the straightforward conversion of L-cysteine (2) into aldehyde 3 (see Scheme 1) constitutes... 

There are numerous abnormalities of cysteine metabolism. Cystine, lysine, arginine, and ornithine are excreted in cystine-lysinuria (cystinuria), a defect in renal reabsorption. Apart from cystine calculi, cystinuria is benign. The mixed disulfide of L-cysteine and L-homocysteine (Figure 30-9) excreted by cystinuric patients is more soluble than cystine and reduces formation of cystine calculi. Several metabolic defects result in vitamin Bg-responsive or -unresponsive ho-mocystinurias. Defective carrier-mediated transport of cystine results in cystinosis (cystine storage disease) with deposition of cystine crystals in tissues and early mortality from acute renal failure. Despite... 

Figure 20. Selective cell targeting via specific monoclonal antibodies and/or antibody fragments directed against cancer cells and linked to the free amino groups of L-cysteine-coated metallic-core magnetic nanoparticles (MNP) (MNP = Co, Fe/Co, size 8-10 nm).

Figure 1.15 AdsorptionofcysteineonAu l 1 0. Molecular model shows the deprotonated thiolate surface species, (a) Model of the reconstructed (1 x 2)-Au l 1 0 surface (b-d) show, respectively, dimers of L-cysteine, D-cysteine, and the two together characteristically rotated relative to the (1 1 0) azimuth. (Adapted with permission from Ref. [57], Copyright 2002, Macmillan Publishers Ltd.)...

In a series of papers, Cook et al.60-63 presented results of the 31P NMR studies of pyridoxal 5 -phosphate dependent enzyme. O-acetylserine sulf-hydrylase is the enzyme which catalyses the final step of biosynthesis of l-cysteine, the replacement of p-acetoxy group of O-acetyl-L-serine by thiol [30] in bacteria and plants. 

Cultured rat vascular smooth muscle cells (VSMCs), grown and prepared for respirometry as described in Doeller et al., 2005 [41], were injected into the respirometer chamber to a concentration of between 105 and 106 cells ml 1. Cell viability remained at >90% throughout experiments. Near 4pM 02, H2S production was stimulated by the addition of L-cysteine and PLP (Fig. 8.8). The initial H2S production rate was approximately 20% of the rat aorta homogenate rate. H2S production rate decreased after the initial rise in H2S concentration, perhaps the result of product feedback inhibition. The addition of the CGL inhibitor BCA showed an effect similar to aorta homogenate. 

Isolated primary rat hepatocytes in the respirometer chamber at 106 cells ml 1 exhibited robust H2S production, achieving concentrations of >20 pM in 30min as the 02 concentration decreased and in the presence of L-cysteine and PLP (Kraus et al., preliminary data, not shown). Inhibitors of both CBS and CGL (amino oxyacetic acid and propargylglycine, respectively) inhibited H2S production, indicating the presence of both enzymes in hepatocytes. 

P. Wang, X.Y. Jing, W.Y. Zhang, and G.Y. Zhu, Renewable manganous hexacyanoferrate-modified graphite organosilicate composite electrode and its electrocatalytic oxidation of L-cysteine. J. Solid State Electrochem. 5, 369-374 (2001). 

A range of L-cysteine derivatives bearing a 1,2,4-triazolyl residue on the sulfur atom has been prepared by the asymmetric Michael addition of 4,5-dialkyl-3-mercapto-l,2,4-triazoles to a nickel Schiff base complex. The enantiomeric excesses of the product aminoacids were measured and found to be greater than 98.5% in some cases <2004TA705, 2004RCB932, 2004IZV894>. 

In structural terms, djenkolic has two units of L-cysteine joined through a CH2 group linked to sulfur atoms. It has also been found in seeds of Albizzia lophanta and Parkia speciosa32 and, as noted earlier, is the source of CS2 in Mimosa pudica (Section 11.1.2.2.2). An enzyme in A. lophanta seeds converted djenkolic acid to an unstable material with a leek-like odor, methylene dithiol 39.92 This was presumably an elimination of aminoacrylic acid 28 via intermediates 37 and 38 (Scheme 13). The methylene dithiol decomposed to H2S and possibly, thioformaldehyde, CH2S the latter might be a source for polysulfides. 

The flour improver would contain sufficient L-cysteine hydrochloride to give 35 mg kg-1 of flour (equivalent to around 27 mg kg-1 of L-cysteine) with sufficient potassium bromate to give 25 mg kg-1 of flour and sufficient ascorbic acid to give 50 mg kg-1 of flour. The above assumes a flour of 12% protein that has had added to it up to 20 mg kg-1 potassium bromate. Alternatively, with an untreated flour all the potassium bromate would be in the improver. 

Zerangue, N. and Kavanaugh, M. P. (1996) Interaction of L-cysteine with a human excitatory amino acid transporter. J. Physiol. 493,419—423. 

Table 10. Comparison of filterpress reactor sizes for the electrosynthesis of L-cysteine hydrochloride. Catholyte = 2 M HC1 at 25°C j = 2 kAm 2 v = 0.35 ms 1 Pb cathode in presence of turbulence promotor DEM cell [13, p. 327J...

Genders JD, Weinberg NL, Zawadzinski C (1991) The direct electrosynthesis of L-cysteine free base, Electroorg Synth (Manuel M Baizer Meml Symp) 1990, (Publ 1991) 273 Chem Abstr 116 (1992) 138606x... 

The reactions of L-cysteine and diethyl 2-formyl-2-halomalonates yielded (thiazolidin-2-ylidene)malonate (545) (84USP626960). 

Zheng L, White RH, Cash VL, Dean DR. 1994. A mechanism for the desulfurization of L-cysteine catalyzed by the nifS gene prodnct. Biochemistry 33 4714-20. 

This enzyme [EC 4.1.99.1], also known as L-tryptophan indole-lyase, catalyzes the hydrolysis of L-tryptophan to generate indole, pyruvate, and ammonia. The reaction requires pyridoxal phosphate and potassium ions. The enzyme can also catalyze the synthesis of tryptophan from indole and serine as well as catalyze 2,3-elimination and j8-replacement reactions of some indole-substituted tryptophan analogs of L-cysteine, L-serine, and other 3-substituted amino acids. 

Scheme 6 Protected Partially Racemic Lanthionine Formation via Michael Addition of L-Cysteine to Dehydroalanine Derivatives133 ...

Although this enzymatic process fills only a niche in the L-lysine market, it is a successful example of a general method for amino acid resolution. It has some superior features compared to the Tanabe L-aminoacylase approach. The L-lysine can be extended to non-protein amino acids such as the use of P. putida aminopeptidase to resolve DL-homophenylalanine to produce precursors for the anti-hypertensive dmg Enalapril. A similar approach has also been used for the production of L-cysteine from DL-2-amino-A2-thiazohne-4-caiboxylate using Sarcina lucea, which is remarkable in that both isomers form L-cysteine. 

Figure 5.7 Screening of microorganisms capable of hydrolyzing DL-amino-2-thiazolme-4-carboxyhc acid has led to a process developed by the Ajinomoto company (currently applied at a scale of 1000 tpa) for the production of L-cysteine (Sano etai, 1977 Yokozeki etal., 1987).

The two heterocyclic rings of thiazolo[3,2-c]quinazolines (273) were formed in one step when 2-ethoxycarbonylaminobenzaldehydes (272) were cyclized with 2-aminothioethanol or esters of L-cysteine (63IJC318 65JIC155, 65JIC220). 

The ring closure of L-cysteine by reaction with aldehydes or ketals 190 194 involving Schiff s base intermediates 195 leads to (4R)-thiazolidine-4-carboxylic acids. Except for formaldehyde and symmetrical ketones, the condensation of L-cysteine with aldehydes or unsymmetrical ketones generates a mixture of epimers, i.e. (25,4R)- and (2R,4R)-thiazolidine-4-carboxylic acid derivatives that can be separated by RP-HPLC or fractional crystallization. 139 ... 

A number of reviews are available in this area several complexes with amino adds are covered in recent general reviews on ligands of biological importance.236,237 The coordination chemistry of L-cysteine and D-penicillamine238 and glutathione239 has been reviewed. 

The biosynthesis of L-cysteine entails the sulfhydryl transfer to an activated form of serine. This pathway to L-cysteine has been most thoroughly studied in E. coli. In the first step an acetyl group is transferred from acetyl-CoA to serine to yield (9-acetylserine (fig. 21.8a). The reaction is catalyzed by serine transacetylase. The formation of cysteine itself is catalyzed by O-acetylserine sulfhydrylase. 

The serine family includes three amino acids Serine, glycine, and cysteine. In this chapter we focused on the synthesis of cysteine, which funnels sulfur into the biochemical world. The biosynthesis of L-cysteine entails the sulfhydryl transfer to an activated form of serine. Most sulfur in nature exists in the inorganic, highly oxidized form of sulfate ion. This sulfur must be reduced to H2S before it can be incorporated into amino acids. 

---