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Synthesis of (plus or minus) [5-{sup 3}H] N'-Nitrosoanatabine, a tobacco-specific nitrosamine

Journal Article · · Journal of Labelled Compounds and Radiopharmaceuticals
DOI:https://doi.org/10.1002/jlcr.630· OSTI ID:825305

Tobacco-specific N'-nitrosamines (TSNA) are a unique class of systemic organ-specific carcinogens. The TSNA are formed by N-nitrosation of nicotine and of the minor tobacco alkaloids after harvesting of tobacco and during smoking. The N-nitrosation of anatabine leads to N'-nitrosoanatabine (NAT; 1-nitroso-1,2,3,4-tetrahydro-2,3'-bipyridyl) which requires in-depth assays in laboratory animals other than the rat. Furthermore, delineation of its tissue distribution and metabolism is needed for structure:activity comparisons with other TSNA and for the assessment of potential human risk from this TSNA. We have, therefore, synthesized (+)[5-3H]NAT. 5-Bromo-3-pyridine-carboxaldehyde was condensed with ethyl carbamate prior to Diels-Alder reaction with 1,4-butadiene to give the racemic anatabine ring system. Hydrolysis followed by reduction with LiAlT4 and nitrosation, led to (+)[5-3H]NAT (60 percent yield, specific activity 266 mCi/mmol, radiochemical purity of >99 percent).

Research Organization:
Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, CA (US)
Sponsoring Organization:
National Cancer Institute of Health. Cancer Center Support Grant P30 CA-17631, Tobacco Carcinogenesis and Chemoprevention Program Project P01-CA 70972, Biomedical Technology Division. National Center for Research Resources Contract P41 RR-01237 (US)
DOE Contract Number:
AC03-76SF00098
OSTI ID:
825305
Report Number(s):
LBNL--50781
Journal Information:
Journal of Labelled Compounds and Radiopharmaceuticals, Journal Name: Journal of Labelled Compounds and Radiopharmaceuticals Journal Issue: 13 Vol. 45; ISSN 0362-4803; ISSN JLCRD4
Country of Publication:
United States
Language:
English

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