Decagram-scale synthesis of GB13, a Galbulimima alkaloid precursor

The Galbulimima alkaloids affect nervous system function in mammals but have proven challenging to study and optimize due to their low and variable abundance in plant matter. Here, we synthesized 12.97 g of the alkaloid GB13 to investigate its conversion to diverse congeners. These divergent transformations required understanding and control of aza-Michael ring-chain tautomerism, which influenced scaffold reactivity profoundly. A series of chemoselective oxidations, including an unusual iodoamine rearrangement, and a C–H amination catalyzed by OsO4, allowed us to identify a single general solution to the class II, III and IV Galbulimima alkaloids.