Cytotoxic Cleistanthane and Cassane Diterpenoids from the Entomogenous Fungus Paraconiothyrium hawaiiense

Hawaiinolides A–D (1–4), four new secondary metabolites including three cleistanthane (1, 3, and 4) and one cassane (2) type of diterpene lactones, were isolated from the crude extract of Paraconiothyrium hawaiiense, a fungus entomogenous to the Septobasidium-infected insect Diaspidiotus sp. The structures of 1–4 were elucidated by nuclear magnetic resonance experiments, and 1 and 3 were further confirmed by X-ray crystallography. The absolute configuration of 1 was assigned via single-crystal X-ray diffraction analysis using Cu Kα radiation, whereas that of 2–4 was deduced via the circular dichroism data. Compound 1 showed significant cytotoxicity against a small panel of five human tumor cell lines, A549, T24, HeLa, HCT116, and MCF-7.