Oxidation-Induced Scaffold Remodeling in Ainsliaea Disesquiterpenoids: Total Synthesis of Macrocephadiolide A

Late-stage oxidations extend terpenoid architectures beyond cyclase-defined boundaries, driving molecular complexity and functional diversity. Disesquiterpenoid biosynthesis illustrates this, as simple monomeric carbocycles evolve into sophisticated dimers through oxidative elaboration. Guided by this logic, we harnessed the oxidase phase of Ainsliaea congeners to generate natural and non-natural privileged scaffolds. A concise, five-step oxidative cascade from ainsliadimer A (3) delivers macrocephadiolide A (5), showcasing oxidation-driven framework reorganization and terpenoid space expansion.