Syntheses of isotope‐labeled tobacco‐specific nitrosamines and their metabolites

We report here on the syntheses of three deuterium‐labeled tobacco‐specific nitrosamines namely [2,4,5,6‐d 4 ]nitrosonornicotine([2,4,5,6‐d 4 ]NNN), 4‐(methylnitrosamino)‐1‐(3‐[2,4,5,6‐d 4 ]pyridyl)‐1‐butanone ([2,4,5,6‐d 4 ]NNK), and 4‐(methylnitrosamino)‐1‐(3‐[2,4,5,6‐d 4 ]pyridyl)‐1‐butanol ([2,4,5,6‐d 4 ]NNAL). A metabolite of NNK and myosmine, 4‐hydroxy‐1‐(3‐[2,4,5,6‐d 4 ]pyridyl)‐1‐butanone, was also synthesized. The synthetic strategy reported here is similar to that reported in the literature for the preparation of corresponding unlabeled compounds. The commercially available [2,4,5,6‐d 4 ]ethylnicotinate was used as starting material. During the course of these syntheses [2,4,5,6‐d 4 ]myosmine and [2,4,5,6‐d 4 ]nornicotine were obtained as stable intermediates. These isotope‐labeled compounds are useful internal standards for quantification of TSNA and their metabolites in smokers in molecular epidemiological studies. Copyright © 2008 John Wiley & Sons, Ltd.