Gold-catalyzed cyclization reaction for the synthesis of biologically relevant polycyclic indole derivatives

The human immunodeficiency viruses (HIV) are two species of retroviruses responsible for AIDS. Despite the approval of several antiretroviral agents for clinical use, the efficacy of these treatments remains compromised because of drug-resistance and side effects associated with prolonged administration. As a result, there is still a high demand from both society and industry for the discovery and development of novel, selective, and safer compounds for HIV therapy. In this context, 5,6-dihydroindolo[1,2-a]quinoxaline has emerged as a promising scaffold, demonstrating potent in-vitro antiretroviral activity against HIV-infected cells. Considering these premises and the continuous interest of our research group in the synthesis and functionalization of complex indole derivatives, we have evaluated the possibility of constructing a new class of indolo[1,2-a]quinoxalines through the cyclization of N-(propa-1,2-dien-1-yl) derivatives under mild and safe catalytic conditions. This transformation exploits the well-established ability of gold to activate allenic bonds and has as main advantages high yields and selectivity. A library of targets with various structural modifications was synthetized, with the rationale in the promising pharmacological potential of this chemical framework, as antifungal and anti-retroviral agents. Moreover, our method showed high flexibility, as we could successfully apply it for the synthesis of 11H-indolo[3,2-c]quinolines, which is another important class of biollogically relevant indole derivatives.