Eucalyptusins A-I, formyl phloroglucinol meroterpenoids with cytotoxic activities from the fruit of Eucalyptus globulus Labill.

Nine undescribed formyl phloroglucinol meroterpenoids (FPMs), eucalyptusins A-I (1-9), and 21 known analogues (10-30) were isolated from the fruit of Eucalyptus globulus Labill. Their chemical structures were elucidated by a combination of NMR and HRESIMS data analyses, and configurations were established by computational calculations of ECD and NMR chemical shifts. Structurally, eucalyptusin A (1) is the first example of a 3,5-diformyl-isopentyl phloroglucinol-monoterpenoid conjugate with a 6/7/6 ring system. Eucalyptusin B (2) is a unique trinorsesquiterpenoid-coupled diformyl-isopentyl phloroglucinol possessing a 6/6/6/6 ring skeleton. Eucalyptusin C (3) possesses a rare 6/6/5/7/3 ring skeleton in the 3,5-diformyl-isopentyl phloroglucinol-aromadendrane derivatives. Cytotoxicity evaluation showed that compound 18 has significant cytotoxic activity against MDA-MB-231, HepG2, and HeLa cell lines with IC50 values of 9.53 ± 0.78, 9.04 ± 0.91, and 7.25 ± 2.17 μM, respectively.