Structure and absolute configuration of parodiolide, a new dimeric sesquiterpene lactone isolated from Mikania parodii Cabrera possessing an uncommon spiro connexion

Abstract

A new dimeric sesquiterpene lactone named parodiolide was isolated from Mikania parodii Cabrera. Its structure and relative stereochemistry were established by HR-MS, 1H- and 13C NMR spectroscopy using 1D and 2D experiments in combination with the use of FT-IR, FT-Raman and UV-Visible spectroscopies. The combination of B3LYP/6-31G* calculations with experimental results revealed its structural and topological properties showing a rare spiro connection, and allowed to establish the absolute configuration of its ten chiral centers. The predicted solvation energy of parodiolide in methanol is -167.9 kJ/mol. Mapped MEP surfaces show nucleophilic sites on two lactone rings while on H atoms of C[dbnd]CH2 and C=C–H groups, electrophilic sites are observed. NBO and AIM studies have shown a higher stability of parodiolide in methanol solution while its gap value in the same medium suggest reactivity comparable to other sesquiterpene lactones, such as cnicin and onopordopicrin. The atomic orbitals of the rings contribute to the increase of the gap value, decreasing their reactivity and potency in solution. Very good correlations were observed when the predicted infrared, Raman, NMR and ECD spectra were compared with the corresponding experimental ones. Complete assignments of the vibration normal modes and the main force constants are also reported for paradiolide in both media. Finally, the ECD spectrum in methanol solution confirms the absolute configuration of parodiolide.