Revised Stereochemistry of Ficifolidione and Its Biological Activities against Insects and Cells

Ficifolidione (1), a
moderately active insecticidal
compound from two species of Myrtaceae, and its derivatives
were synthesized to evaluate their insecticidal activity. X-ray crystallographic
analyses and specific rotation values of ficifolidione and its C-4
(2) demonstrated that the structure of ficifolidione
differs from the reported absolute structure; that is, the C-4 configuration
of ficifolidione should have an S configuration.
The reported insecticidal activity of ficifolidione (1) and its C-4 epimer (2) against adult houseflies (Musca domestica), mosquito larvae (Culex pipiens), and cutworms (Spodoptera litura) was not observed.
The cytotoxicities of ficifolidione and its derivatives (1–4) against four cell lines, Sf9, Colon26, HL60,
and Vero, were also measured because ficifolidione has a phloroglucinol-derived
moiety, a motif that is often present in the structure of cytotoxic
chemicals. Compound 1 exhibited IC50 values
of ca. 32, 9, 3, and 12 μM for Sf9, Colon26, HL60, and Vero
cells, respectively, indicating that ficifolidione possesses selective
cytotoxicity against the four cell lines. In HL60 cells treated with 1, DNA fragmentation and the activation of procaspase 3 were
observed, suggesting that the cytotoxicity is induced by apoptosis.