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Caffeine-derived N-nitroso compounds. II. Synthesis and characterization of nitrosation products from caffeidine and caffeidine acid.

Abstract：

:Caffeine on alkaline hydrolysis produces caffeidine [1-methyl-4-(methylamino)-5-(N-methylcarbamoyl)imidazole] and caffeidine acid [N-[4-(5-carboxy-1-methylimidazolyl)]-N,N'-dimethylurea]. We now report the synthesis and chemical characterization of mononitrosocaffeidine [1-methyl-4-(N-methyl-N-nitrosoamino)-5-(N-methylcarbamoyl)i midazole], dinitroso-caffeidine [1-methyl-4-(N-methyl-N-nitrosoamino)-5-(N-methyl-N-nitrosocarb amo yl) imidazole], and mononitrosamidocaffeidine [1-methyl-4-(methylamino)-5-(N-methyl-N-nitrosocarbamoyl)-Imidazole] based on spectral analysis. The characterization of nitrosated byproducts obtained during the synthesis of these compounds is also presented. Caffeidine is shown to undergo rapid nitrosation in acidic medium to form mononitrosocaffeidine (MNC), an asymmetric N-nitrosamine, and dinitrosocaffeidine (DNC), a N-nitrosamide. Although the reaction proceeds with preferential nitrosation of the amino group in caffeidine, the results also support partial involvement of a mononitrosamide intermediate in the formation of MNC and DNC through transnitrosation of the amino group. The stability data suggest that the nitroso group at the amino nitrogen in DNC influences the reactivity of amide nitroso group. The presence of a trisubstituted ureide moiety in caffeidine acid has been confirmed by NMR nuclear Overhauser effect experiments. Nitrosation of caffeidine acid under acidic conditions produced N,N'-dimethylparabanic acid (DMPA, N,N'-dimethylimidazolidinetrione) as a major product with low amounts of mononitrosocaffeidine and N,N'-dimethyl-N-nitrosourea, whereas nitrosation with NOBF4/pyridine in aprotic medium gave rise to an anhydride, 1,4-dimethyl-4,5-dihydro-5,7-dioxo-1H,7H-imidazo[4,5-d][1,3]oxazine. The nitrosation of methyl ester of caffeidine acid resulted in the formation of a N-nitrosourea derivative, N-[4-(5-carboxy-1-methylimidazolyl)]-N'-nitroso-N,N'-dimethylurea. (ABSTRACT TRUNCATED AT 250 WORDS)

journal_name

Chem Res Toxicol

journal_title

Chemical research in toxicology

authors

Kumar R,Wacker CD,Mende P,Spiegelhalder B,Preussmann R,Siddiqi M

doi

10.1021/tx00031a008

subject

Has Abstract

pub_date

1993-01-01 00:00:00

pages

50-8

issue

eissn

0893-228X

issn

1520-5010

journal_volume

pub_type

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Caffeine-derived N-nitroso compounds. II. Synthesis and characterization of nitrosation products from caffeidine and caffeidine acid.