2-Methyl-2-thiazoline-4-carboxylic Acid: Formation from N-Acetylcysteine and Hydrolysis

Smith, Homer A.; Gorin, George

doi:10.1021/jo01062a043

Cited by 39 publications

(14 citation statements)

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“…At strongly acidic conditions, NAC has been observed to form a five-membered thiazolidine ring through reaction of the thiol with the amide group, which subsequently eliminates H 2 O (catalyzed by H + ) to form 2-methyl-2-thiazoline-4-carboxylic acid (MTC) having a thiazoline ring. , This reaction is termed as the cyclization of NAC. A plausible intermediate in the cyclization of NAC is 2-methylthiazolidine-4-carboxylic acid (MTCA), which readily decomposes through a second-order reaction involving OH – to produce MTC .…”

Section: Introductionmentioning

confidence: 99%

“…They also reported that interconversion of NAC and MTC is possible in various acidic solutions depending on which of the two reactions, that is, cyclization of NAC to MTC or hydrolysis of MTC to NAC, is occurring faster. MTC is unstable and it is readily hydrolyzed to produce NAC in acidic medium. , Although MTC is hydrolyzed to NAC at a very slow rate near pH 7, the open chain form of NAC is thermodynamically more stable at neutral pH compared to MTC . As the acidity increases from pH 7, that is, at lower pH values, the rate of hydrolysis increases to produce more NAC.…”

Section: Introductionmentioning

confidence: 99%

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Monitoring the in Vitro Thiazolidine Ring Formation of Antioxidant Drug N-Acetyl-l-cysteine at Basic pH and Detection of Reaction Intermediates: A Raman Spectroscopic and Ab Initio Study

et al. 2018

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The important cyclization reaction of antioxidant drug N-acetyl-L-cysteine (NAC) has been monitored in vitro at basic pH with the help of time series Raman spectroscopy. The thiazoline ring formation of NAC at acidic pH is a well-known reaction and has been studied extensively. However, the formation of a thiazolidine ring from NAC at basic pH has not been investigated precisely till date. The effect of basicity of the medium on the rate of cyclization has been investigated by studying the reaction at five different basic pH values. Raman signatures of cyclization have been observed with the passage of time and are found to appear faster as the basicity of the medium increases. Ab initio calculations have been done to understand the plausible mechanism of the reaction at basic pH. It is observed that formation of a thiazolidine ring from NAC occurs primarily in four steps, which involve proton abstraction from the thiol (SH) group of NAC and subsequent formation of an S−C bond by a nucleophilic attack of the C−S group on the protonated C−O−H group in NAC. Correlation of the theoretically calculated results with experimental Raman spectral analysis has led to a detailed and proper understanding of this important biochemical reaction.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Monitoring the in Vitro Thiazolidine Ring Formation of Antioxidant Drug N-Acetyl-l-cysteine at Basic pH and Detection of Reaction Intermediates: A Raman Spectroscopic and Ab Initio Study

et al. 2018

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“…Apart from its physiological relevance, l ‐cysteine is also of considerable biotechnological interest. It is used extensively as a nutritional supplement and serves directly as a pharmaceutical (antidote) or as a precursor for therapeuticals, such as N‐acetyl‐ l ‐cysteine (Smith and Gorin, 1961) or the sulphoxides of S‐methyl‐ l ‐cysteine and S‐allyl‐ l ‐cysteine (Duffy, 1980). At present, most of the cysteine is produced by extraction from hydrolysates of keratine.…”

Section: Introductionmentioning

confidence: 99%

Identification of a major facilitator protein from Escherichia coli involved in efflux of metabolites of the cysteine pathway

Daßler

Maier

Winterhalter

et al. 2000

Molecular Microbiology

158

128

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A chromosomal fragment has been identified in a gene bank from Escherichia coli, which augmented the yield of cysteine in an industrial production strain. Subcloning and genetic analysis showed that an open reading frame coding for a product of 299 amino acids (Orf299) was responsible. Orf299 was synthesized in the T7 polymerase/promoter system and exhibited the properties of an integral membrane protein. Mutational interruption of orf299 did not cause a distinct phenotype; however, transformants overexpressing orf299 had lost the ability to grow in minimal medium unless it was supplemented with a source of reduced sulphur compounds, and they excreted considerable amounts of cysteine and O‐acetyl‐l‐serine, especially in the presence of thiosulphate. Most of the cysteine was found to be masked in 2‐methyl‐2,4‐thiazolidinedicarboxylic acid. N‐acetyl‐l‐serine was also present in the medium, but it is open to question whether it represents a primary excretion product. Measurement of the induction status of the cysteine regulon by means of a cysK′–′lacZ gene fusion demonstrated that the regulon is not induced upon growth in the presence of a poor sulphur source and that the introduction of a constitutive cysB allele alleviates this deficiency. The results indicate that orf299 codes for an export pump for different metabolites of the cysteine pathway. Its relation to other efflux systems and the physiological role are discussed.

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“…The same procedure showed that N-acetylcysteine was formed in incubation mixtures containing the enzyme, NADPH, acetylhydrazine, and cysteine. The work of Smith and Gorin (6), which showed that S-acetylcysteine rearranges rapidly at neutralpH values to N-acetylcysteine, suggests that the initial product might have been S-acetylcysteine which subsequently rearranged to the observed product, N-acetylcysteine. In order to study the activation pro- We conducted additional trapping experiments with cysteine and approximately equimolar amounts of acetylhydrazine and [methyl-2H3]acetylhydrazine.…”

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confidence: 99%

Isoniazid and Iproniazid: Activation of Metabolites to Toxic Intermediates in Man and Rat

Nelson

Mitchell

Timbrell

et al. 1976

Science

217

126

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Acetylhydrazine, a metabolite of isoniazid, a widely used antituberculosis drug, and isopropylhydrazine, a metabolite of iproniazid, an antidepressant removed from clinical use because of high incidence of liver injury, were oxidized by cytochrome P-450 enzymes in human and rat liver microsomes to highly reactive acylating and alkylating agents. Covalent binding of these metabolites to liver macromolecules paralleled hepatic cellular necrosis. The metabolites formed from these and probably other monosubstituted hydrazines are reactive electrophiles.

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2-Methyl-2-thiazoline-4-carboxylic Acid: Formation from N-Acetylcysteine and Hydrolysis

Cited by 39 publications

References 0 publications

Monitoring the in Vitro Thiazolidine Ring Formation of Antioxidant Drug N-Acetyl-l-cysteine at Basic pH and Detection of Reaction Intermediates: A Raman Spectroscopic and Ab Initio Study

Monitoring the in Vitro Thiazolidine Ring Formation of Antioxidant Drug N-Acetyl-l-cysteine at Basic pH and Detection of Reaction Intermediates: A Raman Spectroscopic and Ab Initio Study

Identification of a major facilitator protein from Escherichia coli involved in efflux of metabolites of the cysteine pathway

Isoniazid and Iproniazid: Activation of Metabolites to Toxic Intermediates in Man and Rat

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