Cysteine Thioethers from Chloroethylenes<sup>2</sup>

McKinney, L. L.; Eldridge, A. C.; Cowan, J. C.

doi:10.1021/ja01515a034

Cited by 15 publications

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“…Although in principle, different regioisomers of DCVC are possible (Figure 1), DCVC as synthesized according to the method of McKinney (10) is generally thought to be in a trans configuration (I, Figure 1). The chemical mechanism of nucleophilic substitution of a thiolate anion with chloroethylenes in dry liquid ammonia is supposed to be an initial base-catalyzed trans dehydrohalogenation reaction to yield an acetylenic intermediate, followed by a nucleophilic addition to the acetylene moiety (19,20). trans-1,2-Dichloroethylene does not react with thiolates in liquid ammonia, because the trans dehydrohalogenation step is not possible with this compound; however, cis-1,2-dichloroethylene reacted very rapidly with thiolate anions, yielding a disubstituted product which is consistent with the proposed mechanism under these conditions (19).…”

Section: Introductionmentioning

confidence: 99%

Identification of N-acetyl(2,2-dichlorovinyl)- and N-acetyl(1,2-dichlorovinyl)L-cysteine as two regioisomeric mercapturic acids of trichloroethylene in the rat

Commandeur¹,

Vermeulen

1990

Chem. Res. Toxicol.

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The regioselectivity of glutathione conjugation to trichloroethylene (TRI) and the metabolism of its cysteine and N-acetyl-L-cysteine conjugates were investigated in the rat. Intraperitoneal (ip) administration of TRI to rats at a dose of 400 mg/kg resulted in excretion in urine of small amounts of the two distinct regioisomers N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (1,2-DCV-NAC) and N-acetyl-S-(2,2-dichlorovinyl)-L-cysteine (2,2-DCV-NAC). The vicinal (vic) isomer was excreted in a 2 times higher amount (16 nmol) than the geminal (gem) isomer (8 nmol). Intraperitoneal administration of a 1:1 mixture (2.5 mumol/kg each) of the two regioisomers of S-(dichlorovinyl)-L-cysteine (DCVC) to the rat resulted in excretion of the corresponding mercapturic acids in urine, the main fractions being excreted within 8 h after administration. The gem-dichlorovinyl isomer appeared to be acetylated to a higher extend than the 1,2-dichlorovinyl isomer; 73% vs 50% of the dose administered. Intraperitoneal administration of a 1:1 mixture (12.5 mumol/kg each) of the two regioisomers of N-(trideuterioacetyl)-S-(dichlorovinyl)-L-cysteine (DCV-NAC-d3) resulted in excretion of both deuterium-labeled and unlabeled mercapturic acids in urine. The vic isomer was excreted unchanged at a significantly higher percentage, 34% of dose (i.e., still deuterium labeled), than the gem isomer, 17% of the dose. This suggests less efficient metabolism of the vic isomer when compared to the gem isomer. Both regioisomers of DCV-NAC-d3 were excreted in urine unlabeled at 40% of the dose, which indicates that for both isomers deacetylation, followed by reacetylation (resulting in unlabeled DCV-NAC), is an important metabolic pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Introductionmentioning

confidence: 99%

Identification of N-acetyl(2,2-dichlorovinyl)- and N-acetyl(1,2-dichlorovinyl)L-cysteine as two regioisomeric mercapturic acids of trichloroethylene in the rat

Commandeur¹,

Vermeulen

1990

Chem. Res. Toxicol.

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“…Another frequently studied cysteine conjugate is S-(1,2,2-trichlorovinyl)-L-cysteine (TCVC), which is the cysteine conjugate of perchloroethylene. TCVC can be synthesized by the same method as for BTC and DCVC (Support Protocol 3), except that a few modifications are needed to provide for a sufficient yield of material with high enough purity (see McKinney et al, 1959b andRipp et al, 1997).…”

Section: Synthesis Of Btc Dcvc and Tcvcmentioning

confidence: 99%

Methods for Measuring Cysteine S‐Conjugate β‐Lyase Activity

Lash

2007

CP Toxicology

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The cysteine conjugate β-lyase represents activities in cytoplasm and mitochondria catalyzed by at least eleven pyridoxal 5'-phosphate (PLP)-dependent enzymes in various tissues. These enzymes mediate bioactivation of cysteine S-conjugates of several haloalkanes and haloalkenes. The reaction occurs through either a direct β-elimination or a transamination followed by a retro-Michael rearrangement, resulting in the cleavage of a C-S bond. The resultant product is a reactive thiolate that rearranges to form thioacylating species. This unit presents several protocols for the assay of β-lyase activity and includes measurements of product formation and substrate loss as well as fluorescent activity stains. Support protocols describe the synthesis and high-performance liquid chromatography analysis of selected cysteine S-conjugates. Because of the diversity of enzymes that can catalyze a β-lyase reaction, each of the assays presented here may indicate only a portion of the potential β-lyase activity in a given biological preparation.

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Chemistry of acetylenic ethers XLII: A simplified method for the preparation of acetylenic thioethers; a number of new reactions of these compounds

Boonstra

Arens

1960

Recl. Trav. Chim. Pays‐Bas

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Cis ethenylene-1 ,Zbis-thioethers RSCH = CHSR can easily be prepared in liquid ammonia by treating cis or tvans 1,Zdichloroethylene with sodium amide and thiol.From these compounds acetylene thioethers HC =CSR can be obtained by means of sodium amide in liquid ammonia, followed by treatment with one mole of alkyl halide. If two moles of alkyl halide R'X are used, the alkyne thioethers R'C=CSR are formed in satisfactory yield.(Alky1thio)ethynylcarbinols R'R"C(0H)C =CSR are the products of treatment of ethenylene-1,2-bis-thioethers with sodium amide and ketones R'R"C=O in liquid ammonia.Addition of hydrogen chloride to (ethy1thio)ethyne gives l-ethylthio-1 -chloroethylene.Reaction of (ethy1thio)ethyne with acetone under the influence of boron fluoride produces a 50% yield of ethanethiol p,p-dimethylacrylate; similarly 1 -ethylthio-1 -propyne and acetone form ethanethiol a,p,p-tnmethylacrylate.The Mannich reaction of (ethy1thio)ethyne with formaldehyde and diethylamine gives (CzH5)zNCHzC =CSCzHs in very high yield.Long heating of (ethy1thio)ethyne at 90-100" causes the formation of 2-(ethy1thio)thiophene with much tar.Acetylene thioethers HC =CSR' have been obtained in various ways. In this paper we mention only one method, which is of interest in the present context ; for all the other methods we refer to a summary which is shortly to be published 1. 1

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Cysteine Thioethers from Chloroethylenes²

Cited by 15 publications

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Identification of N-acetyl(2,2-dichlorovinyl)- and N-acetyl(1,2-dichlorovinyl)L-cysteine as two regioisomeric mercapturic acids of trichloroethylene in the rat

Identification of N-acetyl(2,2-dichlorovinyl)- and N-acetyl(1,2-dichlorovinyl)L-cysteine as two regioisomeric mercapturic acids of trichloroethylene in the rat

Methods for Measuring Cysteine S‐Conjugate β‐Lyase Activity

Chemistry of acetylenic ethers XLII: A simplified method for the preparation of acetylenic thioethers; a number of new reactions of these compounds

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Cysteine Thioethers from Chloroethylenes2

Cited by 15 publications

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Identification of N-acetyl(2,2-dichlorovinyl)- and N-acetyl(1,2-dichlorovinyl)L-cysteine as two regioisomeric mercapturic acids of trichloroethylene in the rat

Identification of N-acetyl(2,2-dichlorovinyl)- and N-acetyl(1,2-dichlorovinyl)L-cysteine as two regioisomeric mercapturic acids of trichloroethylene in the rat

Methods for Measuring Cysteine S‐Conjugate β‐Lyase Activity

Chemistry of acetylenic ethers XLII: A simplified method for the preparation of acetylenic thioethers; a number of new reactions of these compounds

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Cysteine Thioethers from Chloroethylenes²