Bioactive Constituents Of Liverwort Reboulia Hemisphaerica And Synthesis Of Bibenzyl Derivatives

The bryophytes, which are taxonomically divided into Musci (mosses), Hepaticae (liverworts) and Anthocerotae (hornworts), are morphologically placed between the algae and the pteridophytes (fern). There are about 6 000 species of the liverworts in the world. Among the bryophytes almost all liverworts possess cellular oil bodies that are mainly composed of terpenoids and bisbibenzyls. Many studies indicate that bisbibenzyls exhibit various bioactivities, including antioxidant, cytotoxic, antibacterial, antiviral, anticancer and antifungal activities as well as inhibitory effects on cyclooxygenase, 5-lipoxygenase and calmodulin.In this paper, liverwort Reboulia hemisphaerica (L.) Raddi collected in Kunming Yunnan China was phytochemically investigated. The microtubule depolymerization test showed that Et₂O-soluble fraction is the active fraction. By combination use of LC-DAD-MS/MS and the cell-based bioassay, thirteen compounds have been isolated from the antimicrotubule active fraction of R. hemisphaerica, including eight bisbibenzyls: isomarchantin C (1), riccardin C (2), neomarchantin A (3), marchantin A (4), isoriccardin C (5), riccardin B (6), riccardin D (7), marchantin C (8); three hopane-type triterpenoids:α-zeorin (9), 6α,11α,22-trihydroxyhopane (10), 22-hydroxyhopane (11), andβ-Sitosterol (12), glucose(13). Compounds 3, 4, 5, 6 and 7 were isolated from this plant for the first time. Based on the fragmentation pathways of bisbibenzyls in LC-DAD/MS/MS, the three unconfirmed structures were also proposed accordingly. 4 and 8 were found to be the active compounds ascribed for the microtubule depolymerization activity. This is the first time to prove that bisbibenzyl is the novel class of natural molecule having antimicrotubule activities. Taking these bisbibenzyls as lead compounds, we synthesize fifteen novel bibenzyl derivatives through the chemical reaction of Ullmann, Wittig, and Pd/C reduction. This paper may give some useful information in the development and design of new bibenzyl derivatives in the future.