Lucas W. Hernandez
UIUC
The plant-derived metabolite (+)-7-deoxypancratistatin belongs to a family of densely functionalized and stereochemically complex Amaryllidaceae alkaloids that are known for their potent anticancer activity. However, the molecular complexity and scarce availability from natural sources have proved a challenge in securing sufficient amounts of this natural product for preclinical evaluations. We have developed a scalable, six step synthesis of (+)-7-deoxypancratistatin from benzene using three sequential olefin difunctionalization reactions, which set all six contiguous stereocenters and significantly streamline the overall synthetic route. Moreover, we demonstrated that the key dearomative cis-carboamination of benzene could be extended to other aryl Grignard reagents, delivering diene products in high yields and enantioselectivities.