Chemical Constituents Of Four Liverworts And Their Biological Activities

The bryophytes are taxonomically placed between the algae and the pteridophytes. Morphologically, they are divided into three classes, liverworts (Hepaticae), mosses (Musci), and hornworts (Anthocerotae). The bryophytes have been used as medicinal plants to cure cuts, burns, bacteriosis, pulmonary tuberculosis, neurasthenia, convulsions, scalds, pneumonia, and so on. Almost all species of bryophytes are not damaged by insect, mammals, bacteria, fungi, and viruses. 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, the liverworts Ptilidium pulcherrimum and Frullania inouei collected from Yunnan Province, and Scapania parva and S. ciliata collected from Guizhou Province, were phytochemically investigated. A total of 63 secondary metabolites, mainly including 22 diterpenoids,13 triterpenoids, and 8 bibenzyls, were isolated and identified on the basis of NMR, MS, X-ray, and time-dependent density functional theory (TDDFT) CD calculations.16 of them were new compounds, containing two novel diterpenoids with unprecedented skeletons. The highly methoxylated bibenzyls exhibited moderate cytotoxicity and multidrug resistance (MDR) reversal activities. This work represents the first phytochemical study on the plants of F. inouei, S. parva, and S. ciliate.Separation of the ether extract of the liverwort Ptilidium pulcherrimum afforded 25 compounds, including an undescribed trinortriterpenoid, diospyrolide acetate (1) and a new diphenylmethane derivative, pulcherrimumin (12). The cytotoxicity of pentacyclic triterpenoids 1-11 was evaluated against the PC3, MDA-MB-231, and Hela cells lines. Ursane triterpenoids 8-10 exhibited moderate cytotoxicity against PC3 cells with IC50 values ranging from 10.1 to 39.7?M.From the ether extract of the liverwort Frullania inouei,26 compounds, including four undescribed labdane diterpenoids, 1,2-dehydro-3,7-dioxo-manoyl oxide (26), 1,2-dehydro-7?-hydroxy-3-oxo-manoyl oxide (27),3,7-dioxo-manoyl oxide (28), and 3?-hydroxy-7-oxo-manoyl oxide (29), and a novel chain diterpenoid with an unprecedented C-3/C-8 bond, frullanianin A (33), were isolated. Cytotoxicity tests to human tumor KB, KB/VCR, K562 or K562/A02 cells showed bibenzyls 42-45 inhibited cell proliferation with ID50 values ranging from 11.3 to 49.6?M and overcame the MDR with the reversal fold (RF) values ranging from 3.19 to 10.91 (5?M) for vincristine-resistant KB/VCR and RF values from 4.40 to 8.26 (5?M) for adriamycin-resistant K562/A02 cells, respectively. However, none of the diterpenoids were found to be active (ID50>50?M).Eleven cis-clerodane diterpenoids, including nine new cis-clerodanes, scaparvins A-F (48-52,58) and scapanialides A-C (55-57), as well as two known ones, parvitexins B and C (53 and 54), were isolated from the liverwort Scapania parva.48 is a novel caged cis-clerodane diterpenoid intra-ring bridged with an unprecedented C-6/C-11 bond and intramolecular ketalization at C-12.56 is the first cis-clerodane with a bicycle[5.4.0]undecane skeleton from the liverworts. It was proposed that an enzymatic intramolecular aldol reaction was the key step in the biogenetic pathway of 48.Six compounds, including a fusicoccane diterpenoid, fusicoauritone A (59), and a trachylobane diterpenoid, ent-trachyloban-19-oic acid (60), were isolated from the liverwort Scapania ciliate. Their structures were determined by comparison of their NMR data with those reported in the literatures.