Spiromyrrhenes A–D: unprecedented diterpene–sesquiterpene heterodimers as intermolecular [4 + 2] cycloaddition products from Resina Commiphora that inhibit tumor stemness in esophageal cancer

Abstract

The structures and stereochemistry of spiromyrrhenes A–D (1–4), isolated from Commiphora exudates, were elucidated using NMR and ECD methods. They are the first examples of hepta- and octa-cyclic heterodimers possessing C₃₅ skeletons, for the biosynthesis of which intermolecular [4 + 2] cycloaddition has been proposed. Biological studies show that they suppress tumor stemness in esophageal cancer by inactivating the Hippo/Yap pathway.