Amino-2-thiazoline-4-carboxylate

Sano et al. 127 have found several bacterial strains that are capable of producing l-cysteine from d,l-2-amino-2-thiazoline-4-carboxylate (ATC), an intermediate in the... 

In 1982, Ajinomoto Co. Ltd. industrially applied a three-step enzymatic process to produce L-cysteine from DL-2-amino-2-thiazoline-4-carboxylate (DL-ATC), a starting material of the chemical synthesis of L-cysteine. The enzymes catalyzing this process are DL-ATC racemase, L-ATC hydrolase, and S-carabamoyl-L-cysteine (SCC) hydrolase (Sano et al. 1977, 1979 Sano and Mitsugi 1978 O Pig. 4.4). 

Urine Cystine adduct SCN 2-amino-thiazoline, 4-carboxylic acid HPLC GC-LC SCN (SCN) LOD 3ug/ml 0.3 uM As above... 

P. Lundquist, B. Kagedal, L. Nilsson and H. Ros-ling, Analysis of the cyanide metabolite 2-amino-thiazoline-4-carboxylic acid in urine by high-performance liquid chromatography, Anal. Bio-chem., 228, 27-34 (1995). 

A minor route of metabolism is the oxidation of cyanide to cyanate (CNO-), which occurs via enzymatic and nonenzymatic pathways. The interaction of cystine and cyanide to form 2-amino thiazoline 4-carboxylic acid and its tautomer accounts for approximately 20% of cyanide metabolism. This increases with toxic doses of cyanide. However, the protection conferred by forming cyanate derivatives is limited because of the cell s inability to utilize oxygen during cyanide intoxication. 

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. 

It is worth mentioning here that the spirocyclopropyl-substituted oxazoline-5-car-boxylates 2-172, as well as the corresponding thiazoline-4-carboxylates, can be transformed into cyclopropyl-substituted amino acids, which might act as potential enzyme inhibitors [93] and interesting building blocks for peptidomimetics [94]. 

The Ajinomoto compare has developed a commercial route to L-cysteine, which is currently applied at 1000 tpa scale, by screerring for crrltrrres that produced Lcysteine from DL-2-amino-A 2.thiazoline-4-carboxylic acid, which can be synthesized from 2-... 

Sano, K., Yokozeki, K., Tamura, F., Yasuda, N., Noda, I. and Mitsugi, K. (1977) Microbial conversion of DL-2-amino A -thiazoline-4-carboxylic acid to L-cysteine and L-cystine screening of microorganisms and identification of products. Appl Environ Microbiol, 34, 806-810. 

Bisebromoamide is cytotoxic linear peptide isolated from the marine cyanobacterium Lyngbya sp. (Teruya et al., 2009). Structure of bisebromoamide contains rich unusual amino acid derivatives with D-amino acids, N-methylated amino acids, a brominated tyrosine, a modified 4-methylpro-line, a 2-substituted thiazoline-4-methyl-4-carboxylic acid unit, and a rare... 

In 1978 the conversion of the racemic 2-amino-d2-thiazoline-4-carboxylic acid into L-cysteine, catalysed by Pseudomonas thiazolinophilum cells, was reported [92]. Due to a racemase the overall process is a dynamic kinetic resolution and yields of 95% are obtained in the industrial process (Scheme 6.26) [34]. 

This expectation has been realized in many cases involving the condensation of aldehydes with cyclic a-amino acids, such as proline, pipecoline, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, 1,2,3,4-tetrahydro- -carboline-2-carboxylic acid, and thiazoline-4-carboxylic acid (87CC47). The ylides generated by this route are trapped as the cycloadducts of anti-ylides, for example 111, 112,116, anti- 240, and 241, in cycloadditions using maleimides. 

Similarly, AT-allylthioamides derived from carboxylic acids cyclize to 2-thiazoline derivatives by the action of the bromine-dioxane complex <93PJCI043>. The Mitsunobu reaction can be eflSciently used for preparing 4-carboxy-2-thiazolines from -hydroxy-a-amino acids <92TL2807). Diethyl-... 

Figure 17-14. Enzymatic synthesis of L-cysteine from D,L-2-amino-A2-thiazoline-4-carboxylate.

Chemical Properties of Thiazolidines. - The metal-complexing properties of L-thiazolidine 4-carboxylic acid and of 2-amino-A -thiazoline hydrochloride with Ca Ni ", Mn ", Cu, and Zn have been investigated. ... 

Fig. 8. Alternative catalytic nucleophiles, (a) Tyrosine functions as the catalytic nucleophile in Clan GH-E sialidases and trans-silalidases, with the assistance of a proximal carboxylate amino acid side chain, (b) Anchimeric assistance in hexosaminidases involving reaction of the A -acetyl group of the substrate with the anomeric carbon to form an oxazoline intermediate in the enzyme active site, (c) Sugar thiazolines are noncleavable S-linked inhibitors of hexosaminidases that use an oxazoline intermediate. Enz5mie selectivity can be further tuned by varying i . ...

Wipf et al. have reported that oxazolines and thiazolines can be synthesized by tandem condensation-cydodehydration of carboxylic acids with amino alcohols and aminothiols in the presence of 3-N02C6H4B(0H)2 in moderate to excellent yields (Equation 15) [14],... 

In a weakly alkaline solution, isothiocyanate reacts with the a-amino group of cysteine (Figure 2.64). The reaction of isothiocyanates with cystine leads to the cleavage of disulfide bond (-S-S-) with the formation of cysteine sulfenic acid and a dithiocarbamic acid ester. Dehydration of this ester yields 5-amino-l,3-thiazine-4-one-3-thione derivative and elimination of hydrogen sulfide produces a cyclic 2-thiazoline-4-carboxylic acid derivative (Figure 2.65). Reaction of cystine with thiocyanates (R-S-C=N), formed by spontaneous isomerisation of isothiocyanates, produces disulfide Cys-S-S-R and -thiocyanoalanine, which cyclises to 2-thiazoline derivative (Figure 2.66). 

Sano K, Eguchi NY, Mitsugi K (1979) Metabolic pathway of L-cysteine formation from DL-2-amino-A2-thiazoline-4-carboxylic acid by Pseudomonas. Agric Biol Chem 43 2373-2374... 

Molecular models show that the very large sulfur atoms are readily available for collinear backside displacement. As the cyanide ion approaches the negatively charged COO, this carboxylate group will rotate out of the way and place the amino group in a very close juxtaposition near the sulfur-sulfur bond and the cyanide. It is suggested that the amino group participates and that the thiazoline is formed directly rather than in a two-step process. 

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