PhD defence J. (Jingyao) Li

Substrate exploitation of multicomponent reactions toward diverse scaffolds and applications in medicinal chemistry

Overall, this thesis demonstrates both the targeted exploration of MCR building blocks towards the synthesis of diverse scaffolds and their applications in small molecule drug discovery. In the past decades, researches regarding the methodology investigation and the post-modification of MCRs toward various heterocycles emerge endlessly. Besides the development in the organic chemistry field, the applications of MCRs in medicinal chemistry gain extensive attention on account of their efficiency, low cost, and multiformity properties. The discovery of macrocycles and PROTACs could be beneficial toward the “unarguable” targets, which have flat surfaces and are difficult to bind. The multi-substitution property of MCRs could benefit In the development of these techniques via fragment-based drug discovery. However, multi-substitution always correspond to multi-chiral centers. How to cope with steric hindrance and remote chiral centers toward oriented synthesis is still a big challenge for chemists.

Promotores: prof. dr. A.S.S. Dömling, prof. T.A. Holak