Synthesis and Preliminary Biological Evaluation of Highly Substituted Indoles

Highly substituted indoles are among the most prestigious structures in medicinal chemistry. They found in a vast array of biologically active natural products and pharmaceutical compounds. Due to their relevance, methodologies that allow for the regioselective synthesis of indoles are highly desirable. Herein, we would like to discuss our efforts towards the indole core by exploring the chemodivergent reaction of α-diazo-β-ketoesters and enol ethers. We found that copper (II) catalysts led to the exclusive formation of 1,2-dihydrofuran (DHF) acetals, which served as efficient precursors to the synthesis of indoles. In contrast, Rh (II) catalysts led to the direct formation of regioisomeric indoles. These indoles were then then examined for potential biological activity based on docking models and modified synthetic strategies.