Hydrolysis of thioimidate esters.  Tetrahedral intermediates and general acid catalysis

Chaturvedi, Rama K.; MacMahon, Andrew E.; Schmir, Gaston L.

doi:10.1021/ja01002a029

Cited by 45 publications

(33 citation statements)

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“…It is the major pathway in the hydrolysis of thioimidate esters [20] and mercaptoethanol-catalysed nitrile hydrolysis [21][22][23] at neutral pH. In both cases the product selectivity shifted towards acid at pH < 3.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Nitrile Hydratase Activity of a Recombinant Nitrilase

et al. 2006

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Appreciable amounts of amide are formed in the course of nitrile hydrolysis in the presence of recombinant nitrilase from Pseudomonas fluorescens EBC 191, depending on the a-substituent and the reaction conditions. The ratio of the nitrilase and nitrile hydratase activities of the enzyme is profoundly influenced by the electronic and steric properties of the reactant. In general, amide formation increased when the a-substituent was electron-deficient; 2-chloro-2-phenylacetonitrile, for example, afforded 89 % amide. We found, moreover, that (R)-mandelonitrile was hydrolysed with 11 % of amide formation whereas 55 % amide was formed from the (S)-enantiomer; a similar effect was found for the O-acetyl derivatives. A mechanism that accomodates our results is proposed.

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Section: Mechanism Of Actionmentioning

confidence: 99%

Nitrile Hydratase Activity of a Recombinant Nitrilase

et al. 2006

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“…coo N IX Consistent with this is the observation that the product from the cysteamine reaction absorbs strongly at 270 nm (19). From the known reactivity of related compounds, it is expected that such products will be very susceptible to hydrolysis and attack by nucleophiles, especially when X = S (19)(20)(21). Given (26).…”

mentioning

confidence: 72%

“…To us, the most likely possibility is that the product of the reaction is a metabolic effector. It might act as a reversible effector of some enzymic reactions like cyclic AMP does, but, given the known high reactivity of thiazolines toward nucleophiles (19)(20)(21), it seems more likely that the product would react (Eq. 4) with a nucleophilic group on some (700- (44)(45)(46) of cysteamine to those of glyoxylate (47), but also it links them to the known effects of metabolites and drugs on D-AA oxidase reactions.…”

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confidence: 99%

Reactions of cysteamine and other amine metabolites with glyoxylate and oxygen catalyzed by mammalian D-amino acid oxidase.

Hamilton¹,

Buckthal²,

Mortensen³

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

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, and Lcysteine ethyl ester. Notable physiological amines that do not support a rapid 02 reaction under the above conditions include histamine, serotonin, epinephrine, norepinephrine, spermidine, spermine, and cadaverine. A more detailed kinetic investigation of the reactions involving the first four reactive amines listed above indicated that the cysteamine reaction proceeds at a rapid rate even when cysteamine and glyoxylate are present at less than millimolar concentrations, but greater than millimolar concentrations are needed in the other amine reactions in order to observe a reasonable rate. At low concentrations and pH 7.4, the cysteamine-glyoxylate substrate (presumably thiazolidine-2-carboxylic acid) reacts an order of magnitude faster than any other known D-amino acid oxidase substrate. Considerable circumstantial evidence suggests that the reaction involving cysteamine is occurring physiologically, but the reactions of other amines would be occurring in the cell at a very low rate, if at all. It is proposed that the product of the enzymic reaction may be a metabolic effector that can modify the reactivity of proteins or nucleic acids by covalent attachment. Although the presence of D-amino acid oxidase [D-aminoacid:oxygen oxidoreductase (deaminating), EC 1.4.3.3; D-AA oxidase] activity in mammalian tissues has been known (1, 2) since the early 1930s, the physiological function of the enzyme has remained unknown. The specific reaction catalyzed (3) by the oxidase is the transhydrogenation shown in Eq. I.

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“…Disulfide reactivity towards cysteine in sodium phosphate buffer at pH 6.5 was measured spectrophotometrically on the intermediate nitrile derivative rather than on the final thioimidate ester because this group easily undergoes hydrolysis, which could complicate the calculation (Table 1). 30,31 The reaction of thiols with aryldithio derivatives involves two consecutive steps32-36: (A) Ar-S-S-B + X-SH e Ar-SH + X-S-S-B and (B) X-S-S-B + X-SH e X-S-S-X + B-SH. In the initial step (A), the aryldithio derivative Ar-S-S-B (aryldithiopropionitrile [13][14][15][16][17][18][19] gives, in the presence of the thiolated reagent X-SH (cysteine), the mixed disulfide X-S-S-B and the chromophoric thiophenol Ar-SH.…”

Section: Resultsmentioning

confidence: 99%