Organophosphorus Chemistry: Synthesis of new phosphonic acid derivatives bearing a triazole moiety

The 1,2,3-triazole ring is a privileged building block in synthetic organic chemistry with well established and outstanding properties in medicinal chemistry. On the other hand, there is an extensive interest in synthetic organic methodologies for the construction of new phosphorus-containing molecules, due to the remarkable biological activities of many of these derivatives. In continuation of our search for new potentially bioactive phosphonates, we present herein the preliminary results in the synthesis of new 1,2,3-triazolylphosphonates, combining simple and efficient methodologies developed in our research group.

First, β-ketophosphonates obtained by a procedure that involved the use of copper nanoparticles supported on zinc oxide, were transformed into the corresponding β-azidophosphonates through subsequent reduction, mesylation and azidation steps. Then, a series of new 1,2,3-triazolylphosphonate were synthesized through the multicomponent alkyne-azide 1,3-dipolar cycloaddition catalyzed by copper nanoparticles on activated carbon. The reactions were carried out in water and at a very low copper loading as green conditions, leading to the triazolylphosphonate products in moderate to good yields. Studies about their activity as butyrylcholinesterase inhibitors are underway.