Creation of a nitrosamine library labelled with 14C or tritium

Cancer continues to be a leading cause of global death despite decades of research on its prevention and cure. In the mid-twentieth century, anecdotal evidence began to accumulate that certain chemicals might be cancer-causing and this was followed up with animal model studies. These suspected substances were termed carcinogens and among those investigated were N-nitrosamines (or simply nitrosamines). Interest in nitrosamines is now more than a century old and research continues to explore their biology. Since the 1950’s, steady progress has been made in perfecting chemistry techniques to label interesting compounds with 14C or tritium. However, there have been relatively few reports concerning the synthesis of nitrosamines with these radioisotopes, providing substances which could be valuable in advancing key nitrosamine biology research. Most of the previous literature examples of 14C or tritium labelled nitrosamines related to very specific compounds lacking wider interest and relevance. Also, the resulting products were usually of low specific activity. This paper outlines strategies to accomplish the labelling of more broadly relevant nitrosamines with 14C or tritium at high specific activity. Particularly, a library of 14C labelled nitrosamines with diverse structures was created. Exemplary experimental details are provided for the synthesis of [14C] N-nitrosodiethanolamine as well as the repurification of [ethyl-1-14C] N-nitroso-N-ethylurea. The storage and general stability of 14C nitrosamines is also discussed. Finally, as an example of a typical strategy to prepare a nitrosamine labelled with tritium, the synthesis of [3, 4-3H] N-nitrosopyrrolidine is described in detail.