DFT calculations and dynamic NMR revealed the coalescent NMR phenomena of the 6/6/6/9 tetracyclic merosesquiterpenoids with an unprecedented 9,15-dioxatetracyclo[8.5.3.04,17.014,18]octadecane core skeleton

Two pairs of novel 6/6/6/9 tetracyclic merosesquiterpenoid enantiomers, dauroxonanols A (1) and B (2), possessing an unprecedented 9,15-dioxatetracyclo[8.5.3.0^4,17.0^14,18]octadecane core skeleton, were isolated from Rhododendron dauricum. The nuclear magnetic resonance (NMR) spectra of 1 and 2 showed very broad resonances, and ¹³C NMR spectrum of 1 exhibited only 13 instead of 22 carbon resonances. These broadening or missing NMR resonances led to a great challenge to elucidate their structures using NMR data analysis. Their structures and absolute configurations of 1 and 2 were finally determined by single crystal X-ray diffraction analysis, chiral separation, and electronic circular dichroism (ECD) calculations. Plausible biosynthetic pathways for 1 and 2 are proposed. Conformational analysis, density functional theory (DFT) calculations, and dynamic NMR assigned the coalescent NMR phenomena of 1 and 2 to the conformational changes of the flexible oxonane ring. Dauroxonanols A (1) and B (2) showed potent α-glucosidase inhibitory activities, 2–8 times potent than acarbose, an antidiabetic drug targeting α-glucosidase in clinic.