Synthesis of N-diisopropyl phosphoryl benzyl-tetrahydroisoquinoline, a new class of mitochondrial complexes I and III inhibitors

The synthesis of N-(O,O-diisopropyl phosphoryl)-benzyltetrahydroisoquinoline (3) has been achieved in a ‘one potʹ procedure from imine (2) and diisopropyl-phosphorochloridate (1) generated in situ (POCl3+iPrOH). Compound 3 is the first benzyltetrahydroisoquinoline derivative found to be a potent inhibitor of mitochondrial complexes I and III, and therefore it opens a new perspective with this series of compounds as they can be considered as new class of antitumor agents.