Synthesis of analogues of the marine pyrroloiminoquinone alkaloid wakayin as potential IDO1 inhibitors

Two strategies have been investigated for the synthesis of the marine alkaloid wakayin resulting in the generation of different intermediates of potential value as inhibitors of indoleamine-2,3-dioxygenase (IDO1), a target enzyme involved in the capacity of tumors to escape the immune process. The first one, based on the condensation of a -hydroxyamine on an indoledione for the formation of the bispyrroloiminoquinone framework, has led to wakayin analogues in which one of the pyrrole ring was not completely aromatic. The second, involving the condensation of methyltryptamine on an indoledione and subsequent oxidative cyclisation of the resulting adduct, allowed to define an original method for constructing the bispyrroloquinoline motif. Different analogues comprising a methyl group on the nitrogen of the pyrrole cycle not constituting the pyrroloiminoquinone unit have been obtained.