A modular and streamlined synthetic platform for diverse polyheterocyclic libraries.

Drug discovery is a lengthy, expensive, difficult, and inefficient process with quite a low rate of new therapeutic discoveries from existing molecules or new molecular entities. These projects generally start with a high-throughput screening campaign of commercially available compound libraries

against the target of interest. However in recent years, it became clear that current combinatorial libraries are not enough. As a mission of organic chemists, the development of short and efficient synthetic routes for producing large collections of novel diverse molecular entities is always of great

interest.

Heterocycles composed of elements other than carbon, like oxygen, nitrogen or sulfur, are present in most currently marketed pharmaceuticals and many other being investigated drug candidates. The current project will develop a modular and simple synthetic strategy for the rapid construction of

diverse polyheterocyclic libraries through the combination of multicomponent reactions (MCRs) and translation metal-catalyzed cascade dearomatization processes. The first step is a MCR, which generates diversity from readily available starting materials, whereas the second step, the cascade

dearomatization processes of indoles, naphthols or phenols, led to the generation of highly functionalized heterocyclic libraries. Overall, our proposal will rapidly afford various diverse polyheterocyclic libraries for high-throughput screening in drug discovery.