Chemical Constituents Of Two Liverworts And Their Biological Activities

Bryophytes are taxonomically placed between the algae and the pteridophytes,which are widely considered as the first plant type to successfully make the transition from aquatic to terrestrial and further divided into three phyla as liverworts(Hepaticae),mosses(Musci)and hornworts(Anthocerotae).Liverworts spread widely and possess abundant species around the world.There are more than 6000 liverworts worldwide,about 880 species of which have been found in China.At present,the in-depth scientific researches on liverworts have found that the oil body,a characteristic cell organelle in liverworts,could synthesize and store various aromatic compounds and terpenoids,which are abundant in species and structures.Many secondary metabolites isolated from liverworts exhibited excellent biological activities such as cytotoxicity,insect antifeedant activity,antifungal activity,etc.In this thesis,two species of Chinese liverworts,Heteroscyphus coalitus(Hook.)Schiffner collected from Wuyanling nature reserve in Zhejiang province,and Chandonanthus birmensis Steph collected from Jiulong Mountain nature reserve in Zhejiang Provence,have been chemically investigated.A total of 58 compounds,including 23 undescribed compounds(mainly diterpenoids)isolated and identified on the basis of the combination of normal column chromatography methods,MS,NMR,ECD,and single crystal X-ray diffraction analysis.A labdane diterpenoid from H.coalitus exhibited satisfactory activities against virulence of Candida albicans.Cembrane diterpenoids from C.birmensis displayed moderate cytotoxic activity.43 compounds were isolated from the Chinese liverwort Heteroscyphus coalitus(Hook.)Schiffner,including 18 previously undescribed terpenoids involved a rare harziane type diterpenoid,heteroscyphsic acid A(1);eight ent-clerodane diterpenoids,heteroscyphsic acids B-1(2-9);four labdane diterpenoids,heteroscyphins A-D(10-13);and one guaiane sesquiterpene with ?,?-unsaturated ketone,heteroscyphin E(14);as well as 3 phytane-type diterpenoids,heteroscones B-D(16-18)and a dodecane sesquiterpenoid,heteroscone A(15).The anti-virulence activity of the isolated compounds against Candida albicans DSY654 demonstrated that most of them could block hyphal growth at concentrations ranging from 4-32?g/ml.Further investigation of the most active compound,heteroscyphin D,revealed that it could suppress the ability of C.albicans DSY654 to adhere to A549 cells and form biofilms,and affected the Rasl-cAMP-Efgl pathway,NRGI and UME6 to retard the yeast-to-hyphae transition from qPCR.This work was the first time to report harziane,labdane,phytane,and kaurane diterpenoids from Heteroscyphus coalitus(Hook.)Schiffner,and the harziane was the first time isolated from plants.In addition,the labdane type diterpenoid which could be used as a potential efflux pump substrate was discovered for the first time.15 compounds including five previously undescribed cembrane diterpenoids,chandonanbins A-E(44-48)as well as ten described compounds(50-58)were obtained from Chandonanthus birmensis Step.Seven cembranes were selected to evaluate their cytotoxicities by MTT assay,and some of them exhibited moderate cytotoxic activities towards A2780 and A549.