The combined solid/solution-phase synthesis of nitrosamines: the evolution of the "libraries from libraries" concept

The generation of diverse chemical libraries using the "libraries from libraries" concept by combining solid-phase and solution-phase methods is described. The central features of the approaches presented are the use of solid-phase synthesis methods for the generation of a combinatorial polyamine library. Following cleavage from the resin with HF, the polyamine library was reacted with ethyl nitrite in the solution phase to yield the desired nitrosamine library in good yield and purity. The approaches described enable the efficient syntheses of individual nitrosamines as well as mixture-based nitrosamine libraries.