N-Acylation of Cysteine

Martin, Tellis A.; Corrigan, John R.; Waller, Coy W.

doi:10.1021/jo01019a509

Cited by 13 publications

(8 citation statements)

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“…A number of acetylation methods were investigated while pursuing optimal conditions for the synthesis of N ‐acetylcysteine . Ultimately, the pathway which allowed for the easiest and most efficient purification as well as near quantitative yields was the method of Martin et al .…”

Section: Resultsmentioning

confidence: 99%

“…Ultimately, the pathway which allowed for the easiest and most efficient purification as well as near quantitative yields was the method of Martin et al . (Scheme ) . Thus, L‐[3‐ 13 C]‐cysteine was treated with acetate trihydrate and acetic anhydride to ultimately afford 2( R )‐ N ‐acetyl‐[3‐ 13 C]‐cysteine ([ 13 C]‐NAC; [ 13 C]‐ 1 ) as a hygroscopic, clear, semisolid in 96% yield.…”

Section: Resultsmentioning

confidence: 99%

“…According to a literature procedure for unlabeled material, sodium acetate trihydrate (3.38 mmol, 0.46 g) was added to a thick suspension of L‐[3‐ 13 C]‐cysteine (1.69 mmol, 0.21 g, 99% 13 C, Cambridge Isotope Laboratories) in THF–water (10:1; 0.74 mL) and under a positive pressure of N 2 . The thick mixture was stirred at room temperature for 20 minutes during which time it became more fluid.…”

Section: (R)‐n‐acetyl‐[3‐13c]‐cysteine ([13c]‐1; [13c]‐nac)mentioning

confidence: 99%

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Synthesis of ¹³C‐labeled derivatives of cysteine for magnetic resonance imaging studies of drug uptake and conversion to glutathione in rat brain

Amoyaw

Springer

Gamcsik

et al. 2011

Labelled Comp Radiopharmac

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Effects of neurodegeneration have been linked to inefficient detoxification of free radicals due to lowered concentrations of antioxidants, especially glutathione, in the brain. In the biosynthesis of glutathione, cysteine concentration is generally the limiting factor. Glutathione and cysteine administrations are not effective treatments for neurodegeneration because glutathione inefficiently crosses cell membranes and cysteine is neurotoxic at high concentrations. Prodrugs of glutathione and cysteine may have more favorable uptake and/or toxicity profiles. Three such prodrugs were synthesized with a 13C‐label such that in vivo uptake of each and conversion to glutathione in the brain could be monitored by magnetic resonance imaging. L‐[3‐13C]‐Cysteine was treated with sodium acetate trihydrate and acetic anhydride to give 2(R)‐N‐acetyl‐[3‐13C]‐cysteine ([13C]‐NAC; 96%). Addition of triphosgene to L‐[3‐13C]‐cysteine provided 4(R)‐[5‐13C]‐2‐oxothiazolidine‐4‐carboxylic acid ([13C]‐OTZ; 65%). A four‐step pathway was used to synthesize ethyl γ‐L‐glutamyl‐[3‐13C]‐L‐cysteinate ([13C]‐GCEE). L‐[3‐13C]‐Cysteine was esterified (100% yield) and then cyclized with acetaldehyde to give ethyl 2(R,S)‐methyl‐[5‐13C]‐thiazolidine‐4(R)‐carboxylate (73%) as a mixture of two diastereomers (65:35). The thiazolidine was silylated (bis(trimethylsilyl)trifluoroacetamide) and reacted with N‐phthaloyl‐L‐glutamic anhydride. Treatment with hydrazine afforded ethyl N‐[γ‐4′(S)‐glutamyl]‐2(R,S)‐methyl‐[5‐13C]‐thiazolidine‐4(R)‐carboxylate (48%; 73:27 mixture of diastereomers). This was converted to the desired product, [13C]‐GCEE (49%), using mercury (II) acetate and hydrogen sulfide.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: (R)‐n‐acetyl‐[3‐13c]‐cysteine ([13c]‐1; [13c]‐nac)mentioning

confidence: 99%

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Synthesis of ¹³C‐labeled derivatives of cysteine for magnetic resonance imaging studies of drug uptake and conversion to glutathione in rat brain

Amoyaw

Springer

Gamcsik

et al. 2011

Labelled Comp Radiopharmac

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“…Acetylcysteine [616-91-1], N-acetyl-L-cysteine, C 5 H 9 NO 3 S, M r 163.20, mp 109 -110 C, is made by acylating L-cysteine hydrochloride hydrate with acetic anhydride in the presence of sodium acetate [65]. Acetylcysteine is an effective mucolytic in vitro and in vivo, especially when administered as an aerosol [60], [66].…”

Section: Cysteine Derivativesmentioning

confidence: 99%

Cough Remedies

Bub¹,

Friedrich²

2000

Ullmann's Encyclopedia of Industrial Chemistry

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The article contains sections titled: 1. Introduction 2. Antitussives 2.1. Antitussives Acting on the Central Nervous System 2.1.1. Alkaloids and Derivatives 2.1.2. Morphinans 2.1.3. Arylalkylamines 2.1.4. Basic Esters 2.1.5. Basic Ethers 2.1.6. Piperazine Derivatives 2.1.7. Other Compounds 2.2. Antitussives Acting Mainly Peripherally 3. Expectorants 3.1. Secretolytics and Secretomotorics 3.2. Mucolytics 3.2.1. Cysteine Derivatives 3.2.2. Benzylamines

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“…GSH derivatives such as S-(4-bromobenzyl)GSH have been N-acetylated by the Schotten-Baumann reaction over 1 day with a yield of only 40% N-acetyl-S-(4-bromobenzyl)GSH after a number of purification steps [13]. The disulfide cystine has also been N-acetylated by Ac 2 O [ [14][15][16], but to the best of our knowledge, the synthesis of N-AcHCys has not been reported although N-AcHCys thiolactone is commercially available.…”

Section: Introductionmentioning

confidence: 99%

Rapid high‐yield N‐acylation of aminothiols: N‐acetylglutathione and N‐acetylhomocysteine and their thiol pK_a values

Shen

Bazin

English

2013

Journal of Peptide Science

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Methodology for the rapid N-acylation of aminothiols in aqueous solution using procedures commonly employed in biochemical studies is described here. Glutathione disulfide (GSSG) and homocystine were diN-acetylated in ~100% yield in 0.1 M aqueous NaHCO3 (pH 8.5) at room temperature by 2.5 equiv of the activated ester, N-hydroxysulfosuccinimidyl acetate, an efficient water-soluble acetylating reagent. Following acetone precipitation, diN-acetylGSSG was further purified and desalted on a strong anion-exchange (SAX) cartridge. DiN-acetylhomocystine was simultaneously purified and desalted on a C18 cartridge. The N-acetylated aminothiols were generated using gel-immobilized tris(2-carboxyethyl)phosphine as a reductant, which obviated the need for further purification. Alternatively, disulfide exchange with dissolved dithiothreitol yielded N-acetylglutathione, which was purified on the SAX cartridge. pH titrations of N-acetylglutathione (8.99) and N-acetylhomocysteine (9.66) as well as those of commercially available N-acetylcysteine (9.53) and N-acetylpenicillamine (10.21) yielded pK(a) (SH) values of importance for biological studies.

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N-Acylation of Cysteine

Cited by 13 publications

References 2 publications

Synthesis of ¹³C‐labeled derivatives of cysteine for magnetic resonance imaging studies of drug uptake and conversion to glutathione in rat brain

Synthesis of ¹³C‐labeled derivatives of cysteine for magnetic resonance imaging studies of drug uptake and conversion to glutathione in rat brain

Cough Remedies

Rapid high‐yield N‐acylation of aminothiols: N‐acetylglutathione and N‐acetylhomocysteine and their thiol pK_a values

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N-Acylation of Cysteine

Cited by 13 publications

References 2 publications

Synthesis of 13C‐labeled derivatives of cysteine for magnetic resonance imaging studies of drug uptake and conversion to glutathione in rat brain

Synthesis of 13C‐labeled derivatives of cysteine for magnetic resonance imaging studies of drug uptake and conversion to glutathione in rat brain

Cough Remedies

Rapid high‐yield N‐acylation of aminothiols: N‐acetylglutathione and N‐acetylhomocysteine and their thiol pKa values

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Synthesis of ¹³C‐labeled derivatives of cysteine for magnetic resonance imaging studies of drug uptake and conversion to glutathione in rat brain

Synthesis of ¹³C‐labeled derivatives of cysteine for magnetic resonance imaging studies of drug uptake and conversion to glutathione in rat brain

Rapid high‐yield N‐acylation of aminothiols: N‐acetylglutathione and N‐acetylhomocysteine and their thiol pK_a values