Phenylacetone oxime—An intermediate in the oxidative deamination of amphetamine

Hücker, H.; Michniewicz, Barbara M.; Rhodes, Ryan E.

doi:10.1016/0006-2952(71)90425-4

Cited by 65 publications

(17 citation statements)

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“…Thus, phenylacetone oxime (28) was detected in reaction media containing amphetamine and rabbit liver preparations 5,33,34 . Analogously, (2,4,6-trimethylphenyl)ethylamine 37 gave the corresponding acetophenone oxime (23).…”

Section: A Formation Of Oximesmentioning

confidence: 99%

“…This fostered the notion that, for example, oxime formation from amphetamine might proceed via a hydroxylamine as an alternative intermediate to imine 34 (equation 5). Another possibility was offered by assuming dehydration of an˛,N-dihydroxyamphetamine metabolite to give the oxime 34 . In a study on the biotransformation of a number of˛-substituted amphetamines, oxime levels were found to be highest with the˛-Me compound and substantially lower with amines bearing˛-Et,˛-Pr i or˛-Bu t substituents 126 .…”

Section: A Enzymology Of Oxime Formationmentioning

confidence: 99%

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N‐Oxidative Transformations ofCNGroups as Means of Toxification and Detoxification

Hlavica

Lehnerer

2009

Patai's Chemistry of Functional Groups

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Introduction Chemical Aspects of the N ‐Oxygenation of the C  N Functionality Occurrence of N ‐Oxygenated C  N Functionalities in Natural and Synthetic Compounds and Biological Activity Metabolic in Vivo and in Vitro Formation of N ‐Oxygenated C  N Functionalities Enzymology of the Formation of N ‐Oxygenated C  N Functionalities Further Transformations of N ‐Oxygenated C  N Functionalities Conclusions

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Section: A Formation Of Oximesmentioning

confidence: 99%

Section: A Enzymology Of Oxime Formationmentioning

confidence: 99%

N‐Oxidative Transformations ofCNGroups as Means of Toxification and Detoxification

Hlavica

Lehnerer

2009

Patai's Chemistry of Functional Groups

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“…In the meantime, Hucker et a/. (4) claimed that phenylacetone ketoxime (3a) was the major in vitro metabolite of amphetamine using rabbit liver, and this ketoxime then hydrolyzed to yield the ketone (2a). Subsequently, Beckett and AlSarraj (5) found that 2-hydroxylamino-l-phenylpropane (4a) was, in fact, the primary in t:itro metabolic product of amphetamine using microsomes from various species and these authors showed that the ketone 2a, the oxime 3a, and the alcohol 5a were chemical or metabolic breakdown products of the hydroxylamine 4a.…”

mentioning

confidence: 99%

The Synthesis of Four Possible in vitro Metabolites of the Hallucinogen 1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane (DOM)

Coutts¹,

Malicky²

1974

Can. J. Chem.

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The synthesis of four possible in citro metabolites of the hallucinogen I-(2,s-dimethoxy-4-methylpheny1)-2-aminopropane (DOM) is described. These compounds, 1-(2,5-dimethoxy-4-methylphenyl(-2-propanone, the corresponding oxime, l-(2,5-dimethoxy-4-methylphenyl)-2-propano, and I-(2,sdimethoxy)-4-methylphenyl-2-(hydroxy1amino)propane, could be products of side chain metabolic oxidation of DOM.On decrit la synthese in vitro de quatres mttabolites possibles de l'hallucinogene (dimethoxy-2,s methyl-4 pheny1)-1 amino-2 propane sont decrites. Ces composes, la (dimtthoxy-2,5 methyl-4 phenyl)-I propanone-2, l'oxime correspondante, le (dimethoxy-2,5 methyl-4 pheny1)-1 propanol-2 et le (dimethoxy-2,5 methyl-4 ph6nyl)-l hydroxylamino-2 propane, peuvent Etre des produits de I'oxydation metaboliyue de la chaine lattrale du DOM.[Traduit par le journal]Can. J Chem., 52. 395 (1974) In 1955, Axelrod (1) reported that amphetamine (la) was metabolically oxidized by rat liver microsomes to phenylacetone (2a). In view of this observation, it was of interest to us to determine whether the potent hallucinogen, 1-(2,5-dimethoxy-4-methylpheny1)-2-aminopropane(lb, DOM), a ring-substituted amphetamine, was similarly metabolized to the related ketone (26). A preliminary in vitro metabolism of DOM by means of a rabbit microsomal preparation (10 000 g supernatant) indicated that, compared to amphetamine, very little metabolism took place although a g.1.c. examination of the products showed that very small quantities of some metabolites had formed. T o confirm whether one of these products was the ketone (2b), a synthesis of this compound was undertaken.While this study was in progress, H o and coworkers (2, 3) published their findings on the in ciuo metabolism of DOM in rat and showed that the ketone 2b was not formed in that species. In the meantime, Hucker et a/. (4) claimed that phenylacetone ketoxime (3a) was the major in vitro metabolite of amphetamine using rabbit liver, and this ketoxime then hydrolyzed to yield the ketone (2a). Subsequently, Beckett and AlSarraj (5) found that 2-hydroxylamino-l-phenylpropane (4a) was, in fact, the primary in t:itro metabolic product of amphetamine using microsomes from various species and these authors showed that the ketone 2a, the oxime 3a, and the alcohol 5a were chemical or metabolic breakdown products of the hydroxylamine 4a.These current findings prompted us to extend our studies to the synthesis of the ketone 26, the oxime 3b, the hydroxylamine 4b, and the alcohol 5b, compounds which could be of assistance in the identification of rabbit in vitro metabolites and perhaps help identify the unknown minor in civo metabolites of DOM, described by H o and co-workers (2, 3).The method selected for t h e preparation of 1 -(2,5-dimethoxy-4-methylpheny1)-2-propanone (2b) required 2,5-dimethoxy-4-methylphenylacetic acid (9) asan intermediate.

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“…The reactivity of the resultant oxime has been investigated in rabbit liver homogenates where it was found to be a relatively stable functionality although somewhat susceptible to enzymatic and non-enzymatic hydrolysis, yielding the corresponding ketone (6). Investigations with rat liver homogenates revealed that under anaerobic conditions the oxime is reduced with some degree of stereoselec tivity to yield the corresponding hydroxylamine (5).…”

mentioning

confidence: 99%

“…Oximes have been isolated as major metabolites formed during the oxidative deamination of primary aliphatic amines catalyzed by liver microsomal enzymes (2,6). The reactivity of the resultant oxime has been investigated in rabbit liver homogenates where it was found to be a relatively stable functionality although somewhat susceptible to enzymatic and non-enzymatic hydrolysis, yielding the corresponding ketone (6).…”

mentioning

confidence: 99%

Species Variations in the Metabolism of Acetophenone Oxime by Hepatic Enzymes

Sternson¹,

Hes²

1975

Pharmacology

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The metabolism of acetophenone oxime was investigated in liver homogenates obtained from rats, rabbits, mice and hamsters. Significant species variations were observed in anaerobic metabolism studies both in qualitative and quantitative respects. In all cases, the oxime was initially reduced to the corresponding hydroxylamine. Whereas, the hydroxylamine was resistant to further transformation in rat, subsequent reduction to amine was observed in rabbit, mouse and hamster. Hydroxylamine reduction in rat was however observed in animals pretreated with phenobarbital, 3-methylcholanthrene or carbon tetrachloride. Enzymes catalyzing oxime and hydroxylamine reduction were present in both microsomal and cytosol fractions of liver. Highest reductase activity was observed in rat and mouse. Oxime reductase was not stimulated by either phenobarbital or 3-methylcholanthrene, but was inhibited by carbon tetrachloride.

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Phenylacetone oxime—An intermediate in the oxidative deamination of amphetamine

Cited by 65 publications

References 4 publications

N‐Oxidative Transformations ofCNGroups as Means of Toxification and Detoxification

N‐Oxidative Transformations ofCNGroups as Means of Toxification and Detoxification

The Synthesis of Four Possible in vitro Metabolites of the Hallucinogen 1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane (DOM)

Species Variations in the Metabolism of Acetophenone Oxime by Hepatic Enzymes

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