Supporting informationFull experimental details of previously reported compounds, which are not included in the Experimental section, copies of 1 H NMR and 13 C NMR spectra, HPLC traces. 9-(2-Nitrophenyl)adenine (3a). [17] Obtained as the main product by reaction of 1 with 2a (general procedure I), reaction time was 25 min. Products were anchored on silica gel by
1. 5,6-Methylenedioxy-2-aminoindane (MDAI) is a member of aminoindane drug family with serotoninergic effect, which appeared on illicit drug market as a substitute for banned stimulating and entactogenic drugs. 2. Metabolism of MDAI, which has been hitherto unexplored, was studied in rats dosed with a subcutaneous dose of 20 mg MDAI.HCl/kg body weight. The urine of rats was collected within 24 h after dosing for analyses by HPLC-ESI-HRMS and GC/MS. 3. The main metabolic pathways proceeding in parallel were found to be oxidative demethylenation followed by O-methylation and N-acetylation. These pathways gave rise to five metabolites, namely, 5,6-dihydroxy-2-aminoindane, 5-hydroxy-6-methoxy-2-aminoindane, N-acetyl-5,6-methylenedioxy-2-aminoindane, N-acetyl-5,6-dihydroxy-2-aminoindane and N-acetyl-5-hydroxy-6-methoxy-2-aminoindane, which were found predominantly in the form of corresponding glucuronides and sulphates. However, the main portion of administered MDAI was excreted unchanged. 4. Minor metabolites formed primarily by hydroxylation at various sites include cis- and trans-1-hydroxy-5,6-methylenedioxy-2-aminoindane, 5,6-methylenedioxyindan-2-ol and 4-hydroxy-5,6-methylenedioxy-2-aminoindane. 5. Identification of all metabolites except for glucuronides, sulphates and tentatively identified 4-hydroxy-5,6-methylenedioxy-2-aminoindane was supported by synthesised reference standards.
Phenylnitrenium ion (PhNH(+)) may bind to nucleophiles through nitrogen as well as through C2 or C4 carbons. However, only adducts of the former type have been hitherto reported after its reaction with purine nucleosides. In this study, reactions of N-acetoxyaniline (PhNHOAc), a precursor to PhNH(+), with 2'-deoxyadenosine (dA), 2'-deoxyguanosine (dG), and with DNA in vitro at physiological conditions are described. The reaction of PhNHOAc with dA followed by a hydrolytic deribosylation afforded 8-phenylaminoadenine (C8-PhNHA) together with a smaller amount of N(6)-(4-aminophenyl)adenine (N(6)-4APA). A similar reaction with dG afforded 8-phenylaminoguanine (C8-PhNHG) together with traces of 7-(4-aminophenyl)guanine (N7-4APG). The same adducts were found also in the DNA treated with PhNHOAc, and all of them were identified by comparison of their HPLC retention times and MS(2) spectra with a set of synthesized authentic adenine adducts at C2, C8, N7, and N(6) positions and guanine adducts at C8, N7, and N(2) positions. The newly identified minor adduct, N7-4APG, represents the first proof of arylnitrenium adduction at the N7 position of dG, which is the prominent site of attack by most C-electrophiles.
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