Structures of C25 terpenoids isolated from Chloranthus japonicus

<p> The plants belonging to the genus Chloranthus (Chloranthaceae), which consists of about ten species of undershrubs or perennial harbs, are mainly distributed in the tropical zone of Asia and the temperate zone of East Asia. A large number of monomeric and dimeric sesquiterpenoids have been isolated from the Chloranthus plants so far. Among others, some dimers of lindenane sesquiterpene have attracted widespread interest due to their fascinating structures with a 18-memberd polyester ring and intriguing biological activities such as inhibition of cell adhesion, delayed rectifier K⁺ current inhibition, tyrosinase inhibition, hepatoprotective activity, and anti-HIV activity. </p><p> Chloranthus japonicus (Hitorishizuka in Japanese) has been used as a traditional medicine by the Ainu people, an ethnic minority living in Hokkaido, Japan, for thetreatment of gastrointestinal disorders. During our search for structurally interesting natural products from Chloranthusplants, we have previously reported the isolation of some dimers of lindenane sesquiterpene from the roots of C. spicatus. As part of this research program, constituents of the aerial parts of C. japonics were investigated, resulting in the isolation of four new structurally unique terpenoids, hitorins A–D (1–4). The structures of 1–4 were elucidated on the basis of spectroscopic analyses. </p><p> Hitorin A (1) is a novel C₂₅ terpenoid possessing an unprecedented 6/5/5/5/5/3 hexacyclic ring system including one g-lactone ring and two tetrahydrofuran rings, while hitorin B (2) is a diastereomer of 1. Hitorin C (3) is novel C₂₅terpenoid with a highly complex cage-like heptacyclic ring system structurally related to 1 and 2. Hitorin D (4) is a C₂₂ terpenoid with a 6/6/6/5/5/3 hexacyclic skeleton. Hitorins A–D (1–4) might be generated by condensation of an eudesmane-type sesquiterpene and a thujane-type monoterpene. </p>