Climbing the Oxidase Phase Ladder by Using Dioxygen as the Sole Oxidant: The Case Study of Costunolide.

Natural sesquiterpenoid lactones are prominent scaffolds in drug discovery. Despite the progress made in their synthesis, their extensive oxidative decoration makes their chemo- and stereoselective syntheses highly challenging. Herein, we report our effort to mimic part of the oxidase phase used in the costunolide pathway to achieve the protecting-group-free total synthesis of santamarine, dehydrocostus lactone, estafiatin, and nine more related natural sesquiterpenoid lactones by using dioxygen as the sole oxidant.

Combining the best of both worlds: radical-based divergent total synthesis.

A mature science, combining the art of the total synthesis of complex natural structures and the practicality of delivering highly diverged lead compounds for biological screening, is the constant aim of the organic chemistry community. Delivering natural lead compounds became easier during the last two decades, with the evolution of green chemistry and the concepts of atom economy and protecting-group-free synthesis dominating the field of total synthesis. In this new era, total synthesis is moving towards natural efficacy by utilizing both the biosynthetic knowledge of divergent synthesis and the latest developments in radical chemistry.