N-Hydroxylation of 1-(2,5-demethoxy-4-methylphenyl)-2-aminopropane by rabbit liver microsomes.
Metabolic N-hydroxylation of the potent psychotomimetic amine 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (5) by rabbit liver microsomal preparations has been investigated. Synthetic hydroxylamine 8 was obtained by sequential reduction of the corresponding nitropropene 10 with sodium borohydride followed by zinc reduction of the resulting nitropropane 11. Compound 8 in water (pH 7.4) was rapidly air oxidized to oxime 12; this oxidation was completely blocked by rabbit liver microsomes. Microsomal incubations of amine 5 or its bis(methoxy-d3)hexadeuterio analog 5-d6 resulted in the formation of 8 and 8-d6, respectively, identified as their bis(trifluoroacetyl) derivatives by GLC-MS. Quantitative estimations of metabolite formation employing selected ion monitoring with the aid of an accelerating voltage alternator were accomplished by stable isotope dilution analyses with 5-d6 as substrate and 8-d0 as internal standard. Similar analyses starting with "pseudoracemates" (R)-5-d0:(S)-5-d6 or (R)-5-d6:(S)-5-d0 as substrates established metabolite 8 to be enriched with its R enantiomer.
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism*; D000662:Amphetamines; D000818:Animals; D002849:Chromatography, Gas; D003903:Deuterium; D006898:Hydroxylamines / Q000138:chemical synthesis; D006900:Hydroxylation; D066298:In Vitro Techniques; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D008968:Molecular Conformation; D010091:Oximes / Q000378:metabolism; D011817:Rabbits; D013237:Stereoisomerism
D000662:Amphetamines; D006898:Hydroxylamines; D010091:Oximes; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D003903:Deuterium