Detail of "20960-92-3"

Reference

The hydrolysis and alkylation activities of S-(2-haloethyl)-L-cysteine analogs-evidence for extended half-life

The hydrolysis and alkylation activities of S-(2-haloethyl)-L-cysteine analogs-evidence for extended half-life. Schasteen, Charles S.; Reed, Donald J. (Dep. Biochem. Biophys., Oregon State Univ., Corvallis, OR 97331, USA). Toxicol. Appl. Pharmacol., 70(3), 423-32 (English) 1983. CODEN: TXAPA9. ISSN: 0041-008X. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) A series of S-(2-haloethyl)-L-cysteine derivs.Several reagents with their cas registry numbers 88169-61-3 and 78774-17-1 are used here., which are analogs of the proposed glutathione half-mustard metabolites of dihaloethanes, were synthesized and studied with respect to their hydrolysis and alkylation rates in aq. soln. The trend of relative hydrolysis rates, Br > Cl ? F, paralleled their resp. leaving group abilities; however, a rate increase was seen at pH 8 vs. pH's 6 or 4. Hydrolysis of S-(2-chloroethyl)-L-cysteine [28361-96-8] analogs, where the ionizable groups were blocked [carboxyl esterified and(or) N-acetylated], revealed that the amine moiety was responsible for the increased hydrolysis rate with alk. conditions. Compds. which inhibited the hydrolysis of mustard gas gave similar results with S-(2-chloroethyl)-L-cysteine, a finding which is consistent with the reaction intermediate being a highly charged species. The alkylation rates with 4-(p-nitrobenzyl)pyridine [1083-48-3] were not affected by blocking the ionizable groups. A mechanism of internal cyclization is proposed to explain the accelerated alk. hydrolysis rates noted with S-(2-haloethyl)-L-cysteines but not with the N-acetylated analogs (mercapturic acids). This scheme proposes the formation of 3-(thiomorpholine)carboxylic acid [20960-92-3] as an alternative pathway to the generally accepted hydrolysis reaction. This compd. and not S-(2-hydroxyethyl)-L-cysteine was the identified product following pH 10 hydrolysis. Increased hydrolysis half-time of amine-blocked cysteine analogs vs. parent cysteine analogs may exist with S-(2-haloethyl)glutathione derivs. which may explain the substantial nucleic acid alkylation seen with S-(2-haloethyl) derivs. of glutathione. .