Synthesis of Indole-Derived Allocolchicine Congeners through Pd-Catalyzed Intramolecular C-H Arylation Reaction

The synthesis of several new heterocyclic structural analogs of the natural antimitotic agent allocolchicine is reported. As a key step an intramolecular Pd-catalyzed C–H arylation reaction was used to close the seven-membered ring fused with two electron-rich aryl fragments. The stereostructure of the target compounds was determined by X-ray crystal analysis. The primary biological assessment of the synthesized compounds was carried out on human lymphoma cells. Several allocolchicinoids were determined to possess antiproliferative and apoptosis-inducing activity in the micromolar concentration range.