Synthesis of carbon‐14 labeled 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone

Abstract
The potent carcinogen 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK) is present in tobacco and tobacco smoke. [Carbonyl14C]NNK (6) was synthesized in 27% overall yield. [Carboxyl‐14C] nicotinic acid (1) was esterified with benzyl alcohol and the ester 2 was alkylated by 3‐lithio‐N‐methylpyrrolidin‐2‐one (3). The resulting keto‐lactam 4 was hydrolyzed and decarboxylated by treatment with boiling hydrochloric acid. Nitrosation at pH 4.0 gave [carbonyl‐14C]NNK (6). Carbonyl reduction of [carbonyl‐14C]NNK with either sodium borohydride or cultured rat liver slices gave [carbinol‐14C] 4‐(methylnitrosamino)‐1‐(3‐pyridyl) butan‐1‐ol‐(7).

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