Eugenilones A−N: sesquiterpenoids from the fruits of Eugenia uniflora.

(+) and (−)-Eugenilones A−K, 11 pairs of undescribed enantiomeric sesquiterpenoids, together with three undescribed biogenetically related members eugenilones L−N, were discovered from the fruits of Eugenia uniflora Linn. (Myrtaceae). Structurally, eugenilones A−D were four caged sesquiterpenoids featuring 9,10-dioxatricyclo [6.2.2.02,7]dodecane, 11-oxatricyclo [5.3.1.03,8]undecane, and tricyclo [4.4.0.02,8]decane cores, respectively. Eugenilones E−K were eudesmane-type sesquiterpenoids, while eugenilones L−N were epoxy germacrane-type sesquiterpenoids. Notably, eugenilones A−K were efficiently resolved by chiral HPLC to give 11 pairs of optically pure enantiomers. The structures and absolute configurations of eugenilones A−N were determined through spectroscopic analyses, X-ray crystallography, and ECD calculations. The putative biosynthetic pathways for these undescribed isolates were proposed. Moreover, eugenilones A and E exhibited significant anti-inflammatory effects by inhibiting LPS-stimulated NO overproduction in RAW264.7 cells (IC 50 values of 4.89 ± 0.37 μM and 20.89 ± 1.49 μM, respectively) and TNF- α -induced NF- κ B activation in HEK293 cells (IC 50 values of 10.97 ± 1.03 μM and 28.63 ± 1.59 μM, respectively). Eugenilones A−N (1 − 14), 14 undescribed sesquiterpenoids, including four members with rare caged ring systems, were isolated and identified from the fruits of Eugenia uniflora. It is noteworthy that compounds 1 − 11 existed as 11 pairs of enantiomers and were successfully resolved by chiral HPLC. Furthermore, compounds 1 and 5 showed significant anti-inflammatory effects. [Display omitted] • Fourteen undescribed sesquiterpenoids, including four with rare caged ring systems, were isolated from Eugenia uniflora. • Eugenilones A−K existed as 11 pairs of enantiomers, which were uncommon in natural sesquiterpenoids. • Eugenilones A and E showed significant anti-inflammatory effects in RAW264.7 and HEK293 cells. [ABSTRACT FROM AUTHOR]