Chemical studies on tobacco smoke XXIII. Synthesis of carbon‐14 labelled myosmine, nornicotine and N′‐nitrosonornicotine

Abstract

SUMMARY dl-Nornicotine-2 '-14C was synthesized i n four steps. Nicotinic acid (carboxylnicotinate (carbo~ycyZ-~~C). The ester was condensed with 3-lithio-gtrimethylsilyl-2-pyrmlidone t o give 3-nicotinoyl-g-trimethylsilyl-2-pyrrolidone (ketone carbonyti n concentrated hydrochloric acid to give myosmine-2 '-I4C. Reduction o f myosmine-Zr14C gave nornicotine-2'-14C. Reaction o f nornicotir~e-Z'-'~C in hydrochloric acid with sodium n i t r i t e gave g ' -n i t r o s o n o r n i~o t i n e -Z ' -~~C . Purification of Labelled myosmine, nornicotine, and-N'-nitrosonornicotine oas accomplished by prepamtive t h i n lager chmmztography. CI was f i r s t e s t e r i f i e d with diazomethane t o yield methyl14 C), which was hydrolyaed and decarboxylated

Analysis of O6-[4-(3-Pyridyl)-4-oxobut-1-yl]-2′-deoxyguanosine and Other DNA Adducts in Rats Treated with Enantiomeric or Racemic N′-Nitrosonornicotine

“…19, 20 POB-DNA standards and deuterium labeled internal standards were synthesized previously in our laboratory. 17, 21–23 Puregene DNA purification solutions, proteinase K and RNase A were purchased from Qiagen (Valencia, CA).…”

Metabolism and Pharmacokinetics ofN′-Nitrosonornicotine in the Patas Monkey

“…1 is a tobacco-specific nitrosamine formed by nitrosation of the tobacco alkaloids nornicotine and nicotine (Hu et al, 1974;Hecht et al, 1978). It is the most prevalent strongly carcinogenic nitrosamine in smokeless tobacco products, such as chewing tobacco and snuff, and occurs in substantial quantities in cigarette smoke (Hoffmann et al, 1994).…”

“…Racemic [5-3 H]NNN (1.9 Ci/mmol, tritium at the 5-position of the pyridine ring) was purchased from ChemSyn Laboratories (Lenexa, KS). NNN and its metabolites were synthesized (McKennis et al, 1964;Hu et al, 1974;Chen et al, 1978;Hecht et al, 1980;Upadhyaya et al, 2001). trans-3Ј-Hydroxycotinine and norcotinine were purchased from Toronto Research Chemicals (Toronto, ON, Canada).…”

Analysis of N′-nitrosonornicotine and its metabolites in rabbit blood with liquid chromatography/tandem mass spectrometric method

“…N -nitrosonornicotine (NNN) is a tobacco-specific nitrosamine (TSNA) formed by nitrosation of the tobacco alkaloid and metabolite nornicotine [1]. NNN can cause tumors of the esophagus and nasal mucosa in rats, respiratory tract in hamsters, lung in mice [2] and is likely to play an important role as a cause of esophageal cancer in smokers and oral cavity tumors in people who use smokeless tobacco products [3].…”