Unsaturation-Controlled Translactonization Enables Biomimetic Access to the A-Ring Lactone Motif of 3,4-Seco-nortriterpenoids

Abstract 3,4-Seco-nortriterpenoids such as correolide and galphimine B contain a characteristic seven-membered unsaturated lactone. Using friedelin as a model substrate, we examined a proposed biosynthetic sequence involving Baeyer–Villiger oxidation and translactonization. The saturated hydroxy lactone resisted translactonization, whereas α,β-unsaturation reversed the preferred lactone connectivity and afforded the targeted A-ring lactone motif. DFT calculations supported this thermodynamic reversal, establishing α,β-unsaturation as a determinant of lactone connectivity.