Enantioselective Synthesis of Cyclic Thioureas via Mannich Reaction and Concise Synthesis of Highly Optically Active Methylthioimidazolines: Discovery of a More Potent Antipyretic Agent

Abstract

AbstractDrug lead synthesis by the rapid construction of chiral molecular complexity around the biologically relevant framework using a highly efficient strategy is a key goal of organic synthesis. Herein, a highly efficient and convenient strategy that allows the rapid synthesis of highly optically active methylthioimidazolines through the novel rosin‐derived thiourea‐catalyzed asymmetric synthesis of cyclic thioureas with high levels of enantio‐ and diastereoselectivity (up to 99% ee, and 20:1 dr) via Mannich reaction is described fior the first time. Several of the new methylthioimidazolines showed extremely promising antipyretic activity in the development of neuroinflammation through preliminary biological studies. Additionally, to gain a better understanding of the structural stability‐activity relationships, explicit molecular dynamics (MD) simulations in water at room temperature and at body temperature were investigated.