2- -1,3-thiazoline-4-carboxylic

Closure of the (5)-2-methylcysteine compound 19 (see Scheme 3) provides the thiazoline carboxylic acid 38. For the addition of the next thiazoline ring, the carboxylic acid 38 has to be converted to a thiocarboxylic acid. Fukuyama... 

The synthesis of 9H-benzo[2,l-e]thiazolo-[2,3-c]-as-triazine (401) was achieved by oxydative cyclization of 2-imino-3-(o-aminophenyl)-4-phenyl-4-thiazoline (718, 719). This latter reacts also with paraformaldehyde in hot toluene yielding 3-phenyl-9H.10H-benzo[l,2-/]thiazolo-[2,3-d][l,3,5]triazepine (402) (720). This heterocyclic sytem is also formed when carboxylic acids replace paraformaldehyde (Scheme 230) (721). 

Treatment of benzoquinone with ethyl-4-methyl-A-4-thiazoline-2-thione-5-carboxylate yields ethyl-2-(2.5-dihydroxyphenylthio)-4-methyl-5-thiazolyl carboxylate (78) (Scheme 37) (165). 

Thiazole carboxylic acid hydrazides were prepared in a similar way (444, 445). Thus by refluxing thioacetamide or thiobenzamide with y-bromoaceto acetic ester arylhydrazones (83) for several hours in alcohol the 4-carboxythiazole derivatives (84) listed in Table II-ll were obtained (Scheme 36) (656). This reaction is presumed to proceed via dehydration of the intermediate, thiazoline-S-oxide. 

Serratia mane seem 3,4-dehydro-Pro prodegradation , thiazoline-4-carboxylate/ azetidine-2-carboxylate (transduction) 75 145... 

CHROMIUM TRIOXIDE-PYRIDINE COMPLEX, preparation in situ, 55, 84 Chrysene, 58,15, 16 fzans-Cinnamaldehyde, 57, 85 Cinnamaldehyde dimethylacetal, 57, 84 Cinnamyl alcohol, 56,105 58, 9 2-Cinnamylthio-2-thiazoline, 56, 82 Citric acid, 58,43 Citronellal, 58, 107, 112 Cleavage of methyl ethers with iodotri-methylsilane, 59, 35 Cobalt(II) acetylacetonate, 57, 13 Conjugate addition of aryl aldehydes, 59, 53 Copper (I) bromide, 58, 52, 54, 56 59,123 COPPER CATALYZED ARYLATION OF /3-DlCARBONYL COMPOUNDS, 58, 52 Copper (I) chloride, 57, 34 Copper (II) chloride, 56, 10 Copper(I) iodide, 55, 105, 123, 124 Copper(I) oxide, 59, 206 Copper(ll) oxide, 56, 10 Copper salts of carboxylic acids, 59, 127 Copper(l) thiophenoxide, 55, 123 59, 210 Copper(l) trifluoromethanesulfonate, 59, 202... 

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]. 

An enantioselective synthesis of both (R)- and (5)-a-alkylcysteines 144 and 147 is based on the phase-transfer catalytic alkylation of fert-butyl esters of 2-phenyl-2-thiazoline-4-carboxylic acid and 2-ort/ro-biphenyl-2-thiazoline-4-carboxylic acid, 142 and 145 <06JOC8276>. Treatment of 142 and 145 with alkyl halides and potassium hydroxide in the presence of chiral catalysts 140 and 141 gives the alkylated products, which are hydrolyzed to (R)- and (S)-a-alkylcysteines 144 and 147, respectively, in high enantioselectivity. This method may have potential for the practical synthesis of chiral a-alkylcysteines. 

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

A)-5,5-Dimethyl-thiazoline-4-carboxylic acid reacted efficiently with alkyl and aryl isothiocyanates to give bicyclic thiohydantoins 418. A similar diastereo- and regioselective cyclization of chiral l,3-thiazolidine-2,4-dicarboxylic acids was also reported (Equation 191) <1996JHC1099, 1998HCA744>. 

Esters of -hydroxy- or )8-mercapto-AAs react with n-butyl isonitrile to give 5-substituted methyloxazoline (or thiazoline)-4-carboxylates in the presence of PdCla as a catalyst (74SC97). The enamine-protected AAs were also tranformed into oxazolidin-5-ones after reaction with alkyl chloroform-ates (Scheme 28) (75S724). 

The stmcture of pyochelin (for a detailed bibliography, see (57)), a secondary siderophore of Pseudomonas aeruginosa and of Burkholderia cepacia was established (75) as 2-(2-o-hydroxyphenyl-2-thiazolin -yl)-3-methylthiazolidine-4-carboxylic acid. It consists of a mixture of two easily interconvertible stereoisomers (pyochelin I and II) differing in the configuration of C-2". They can be separated by chromatography, but in methanolic solution (not in DMSO) the equilibrium (ca. 3 1) is restored quickly. For a discussion of the mechanism of isomerization, see (57, 577). 

A short and efficient syntl thiazoline-5-carboxylates 143 and benzamides as well as developed (Scheme 46) [53, Michael addition of 142-X acr conditions followed by an in chlorine substituent. Cl + C02Me 1-Me, 2-Me lesis of 4-spirocyclopropane-annt and 144 from chlorocyclopropylid benzthioamides 142-X, respecti 72, 87]. This domino transforma OSS the double bond of 1-Me or 2-tramolecular nucleophilic substiti NaH, DMF. X Reaction dated oxa- and eneacetates 1,2 vely, has been tion involves a Me under basic Lition of the a- C02Me 143, 144 ... 

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... 

Numerous studies of the photoreactions of dihydrofurans have been described. On irradiation 2,3-dihydrofurans are known to undergo conversion to acylcyclopropanes by a pathway involving initial carbon-oxygen bond homolysis. The /i-enamino ester (162), for example, affords the cyclopropane (163) on triplet-sensitized irradiation.138 Similar transformations have been observed in 2,2,4-triacyl-2,3-dihydrofurans,139 and a synthesis of a cis-trans mixture of chrysanthemum carboxylic acid has been accomplished in this way.140 The conversion of the 2-thiazolines(164) to the iV-alkenylthio-amides (165) presumably involves an analogous carbon-sulfur bond homolysis, followed by a 1,2-hydrogen shift in the resulting biradical (166).141... 

The group of Jew and Park successfully utilized dihydrocinchonidine-derived 6f as an efficient catalyst for the asymmetric alkylation of o-biphenyl-2-oxazoline- and o-biphenyl-2-thiazoline-4-carboxylic acid tert-butyl esters (16a and 16b) under mild solid-liquid phase-transfer conditions (Scheme 2.13) [32,33]. These reactions are... 

Jew and Park also succeeded in expanding the methodology to the similar asymmetric alkylation of 2-phenyl-2-thiazoline-4-carboxylic acid ester 55 to furnish optically enriched a-alkyl cysteine derivatives 56 (Scheme 5.27) [29]. 

An alternative electrochemical route to the thiazoline-azetidinone 36 also has been developed. Carboxylic acid 39 prepared from penicillin G can be converted to 36 via 40 by electrochemical decarboxylative acetoxylation followed by hydrolysis (Scheme 2-13)The electrolysis of 39 in an AcOH/DME—AcONa—(C) system at 0 °C... 

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). 

IV-Allylthioureas and thioamides (385) undergo an acid-catalyzed cyclization to A2-thiazolines (387). The reaction proceeds through the carbenium intermediate (386 Scheme 236) (70JOC3768). In a similar way, a-isothiocyanatoacrylates (388) add alcohols or thiols affording intermediate a-thioacylaminoacrylates (389) which cyclize under acid or basic conditions to 2-substituted A2-thiazoline-4-carboxylates (390 Scheme 237) (76LA1997). 

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]. 

The synthesis of the oxazole compound 45 starts with the coupling of the N-protected (/ )-methylcysteine compound 18 with threonine terf-butyl ester using bis(2-oxo-3-oxazolidi-nyl)phosphinyl chloride (BOP-Cl) [15] as a coupling reagent. Jones oxidation of the threonine hydroxy group leads to the ketoamide 44. The desired oxazole ring is closed by treatment with thionylchloride/pyridine. After deprotection, the oxazole, compound 45 is obtained. In the next step the oxazole compound 45 is coupled with the tris(thiazoline) compound 43 to yield the thioester 46. Now Fukuyama closes the fourth and last thiazoline ring (46 47). After conversion of the carboxylic acid function into a methyl-... 

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