1079950-13-2Relevant academic research and scientific papers
Syntheses of D-labelled oxidative metabolites of acrylamide and acrylonitrile for the quantification of their toxicities in humans
Belov, Vladimir N.,Korneev, Sergei M.,Angerer, Juergen,De Meijere, Armin
, p. 4417 - 4425 (2008)
Syntheses of the labelled oxidative metabolites of acrylamide and acrylonitrile - reference compounds for the evaluation of human exposure to important toxicants - are reported. For that, L-cystine tert-butyl ester was acetylated and the product reductively cleaved to L-cysteine tert-butyl ester, which reacted with carbamoyl[D3]oxirane (obtained from [D 3]acrylonitrile and 30% aq. H2O2 at pH = 7.0-7.5) and afforded a separable mixture of tert-butyl N-acetyl-S-(2-hydroxy-2- carbamoyl[ D3]ethyl)cysteinate and tert-butyl N-acetyl-S-(1- carbamoyl-2-hydroxy[D3]ethyl)cysteinate (ca. 9:1). Removal of the tert-butyl group in these intermediates with aq. HCl gave the final deuterated internal standards with carbamoyl residues. Protection of the secondary hydroxy group in the major intermediate with tBuMe2SiCl/imidazole in DMF followed by dehydration of the carbamoyl group (trifluoroacetic anhydride/pyridine in CH2Cl2) and stepwise removal of the tert-butyl and tBuMe2Si protecting groups (TFA, Et3SiH, CH2Cl2; aq. HF in MeCN) yielded N-acetyl-S-(2-cyano-2- hydroxy[D3]ethyl)cysteine. Monoprotection of [D4]ethylene glycol with tBuMe2SiCl and NaH in THF, oxidation to tBuMe 2SiOCD2CDO, conversion to tBuMe2SiOCD 2CD(OH)CN and tBuMe2SiOCD2CD(OTs)CN followed by nucleophilic substitution of the tosyloxy group with N-acetyl-L-cysteine (MeOD, Et3N) and deprotection with 4 M HCl in dioxane resulted in N-acetyl-S-(1-cyano-2-hydroxy[D3]ethyl)cysteine. All transformations (except the last but one) gave the respective products in good yields. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
