Stereodivergent Synthesis of 6,12-Guaianolide C1 Epimers via a Rationally Designed Oxy-Cope/Ene Reaction Cascade.

Nature synthesizes epimeric C1 guaianolide congeners, key components of major natural product classes, through a single structurally flexible macrocyclic germacranolide core. Our rationally designed elemanolide-type scaffold () now mimics this natural process, enabling the stereodivergent synthesis of both C1 epimers of 6,12-guaianolide lactone motifs. An oxy-Cope/ene cascade acts as the key step of this process, generating two distinct conformers of an intermediate germacranolide, each leading to a specific C1 epimer.

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.