Chemical Constituents Of Six Liverworts And Their Biological Activities

The bryophytes [Musci (mosses), Marchantiophyta (liverworts) and Anthocerotae (homworts)], are morphologically placed between the algae and the pteridophytes (fern). Bryophytes, considered being the first plant type to successfully make the transition from water to land, have yielded various secondary metabolites with interesting chemical structures and significant biological activity. Now the bryophytes have been well known as a source of biologically active, naturally occurring compounds. As a Chinese folk medicine, the bryophytes have been used as medicinal plants to cure cuts, burns, bacteriosis, pulmonary tuberculosis, neurasthenia, convulsions, scalds, pneumonia, and so on. There are more than6000liverworts worldwide, among about880species of which have been found in china. Among the bryophyte species, liverworts have been phytochemically investigated in most detail because they possess cellular oil bodies, which are rich sources of lipophilic terpenoids and aromatic compounds, while the other two classes do not contain such oil bodies. Many of the isolated compounds from liverworts exhibit attractive biological activities.In this research of six Chinese liverworts, Marchantia polymorpha collected from Sichuan Province, Conocephalum japonicum, Bazzania albifolia, Pedinophyllum interruptum, and Scapania ciliata collected from Guizhou Province, and Apomarsupella revolute collected from Yunnan Province were phytochemically investigated. A total of72secondary metabolites were isolated and identified on the basis of NMR, MS, X-ray, and time-dependent density functional theory (TDDFT) CD calculations, containing24new compounds. The bisbibenzyls exhibited moderate cytotoxicity and antifungal activities. Activity test showed that the bisbibenzyls exhibited moderate cytotoxicity and the highly oxygenated ent-pimarane-type diterpenoids inhibited germination of the Arabidopsis thaliana seeds. This work represents the first phytochemical study on the plants of Bazzania albifulia, Pedinophyllum interruptum, and Apomarsupella revolute.From an Et2O extract of M. polymorpha,23compounds were isolated by repeated column chromatography on Si gel and Sephadex LH-20, followed by semipreparative high-performance liquid chromatography (HPLC), which were characterized as10bisbibenzyls,1bisbibenzyl,2naphthalenes,2single benzene derivatives,6triterpenoids and2steroids. The cytotoxicity of10bisbibenzyls was evaluated against eight human tumor cells lines. Neomarchantin A (3) and Riccardin C (8) exhibited significant cytotoxicity against Human lung tumor A-549cell.From the ether extract of the liverwort C. japonicum,16compounds, including two undescribed dimeric ArC2derivatives, cis-and trara-1,2-bis(3,4-dimethoxyphenyl)cyclobutane (24and25), one new monoteipenes esters,2α,5β-dihydroxybomane-2-cis-cinnamate (26), along with eight known compounds were isolated. All the structures were established by extensive spectroscopic analysis. Up to date, this is the second report on naturally occurring cyclobutane derivatives isolated from the liverworts. Suggested biosynthetic pathway for24and25was proposed. Cytotoxicity of monoterpenes esters and bisbibenzyls to human tumor KB cell was tested by MTT.18compounds were isolated from the ether extract of the liverwort B. albifolia (36-51), including one undescribed6,7-secofusicoccane-type diterpene, albifolione (36), and one new aromadendrane-type sesquiterpenoid ketone, methyl-2-oxo-1(10),3-dien-aromadendren-12-oate (37). Compound36was the first naturally occurring diterpenoid with a cleaved fusicoccane framework. Preliminary bioassay found that main compound45exhibited moderate antifungal effects with the MIC values of16μg/ml. Compound46showed quite strong cytotoxicity against the human tumor cell line MCF-7, with IC50value of5.63μM.Ten highly oxygenated ent-pimarane-type diterpenoids pedinophyllols A-J (52-62) have been isolated from the Chinese liverwort Pedinophyllum interruptum. Their structures were determined by comprehensive analysis of spectroscopic data together with single-crystal X-ray diffraction analysis. The absolute configuration was achieved by analysis of the CD spectra and by quantum chemical CD calculations. Allelopathic test showed that some of these diteipenoids inhibit germination of the Arabidopsis lhaliana seeds. Among them, compound52significantly retarded the Arabidopsis seeds germination at7.8μg/mL, which indicated that they could also play a role as allelochemicals for liverwort to defense against other plants.Phytochemical investigation of the Et2O extract of liverwort Apomarsupella revolute led to isolation and identification of five new eudesmane-type and a deacetylation product (63-68), two of which were trinorsesquiterpenoids. Compound63exhibited weak antifungal effects with the MIC value of128μg/mL. The combination treatment of63and FLC showed additive effect against C. albicans. This work shed lights on chemotaxonomy and chemical ecology of this liverwort species.Four clerodane diterpenoids (69-72) were isolated from the liverwort Scapania ciliate.69is the first clerodane quadrinorditerpenoid from the liverworts. Their structures were determined by NMR, X-ray, and comparison of their NMR data with those reported in the literatures.