Modular Total Synthesis of the 5/5-Spirocyclic Spiroindimicins

Total syntheses of the 5/5-spirocyclic indoline alkaloids spiroindimicins B, C, D, E, F, and G have been achieved via a modular approach. Our route features direct coupling of halogenated pyrrolemetal and isatin partners, Suzuki coupling to append the indole unit, Lewis acid-mediated spirocyclization, and divergent functionalization to various family members. These syntheses are concise (6–7 steps from commercial materials), scalable, and highly amenable to analogue synthesis. Further studies of the antiparasitic properties of this class have revealed promising activity against T. brucei for certain congeners. Together with our prior approach to 6/5-family members, our work constitutes a synthetic solution to all known spiroindimicin natural products.