Chemical Constituents Of Four Liverworts And Their Biological Activities

Bryophyta belongs to the most primitive higher plant, which include Musci (mosses), Marchantiophyta (liverworts) and Anthocerotae (hornworts). They are traditionally used in China as folk medicines for the treatment of skin ulcer, burns, pain and swelling from injuries, external bleeding, and related diseases. There are more than 1600 liverworts worldwide, among about 800 species of which have been found in china. Various types of lipophilic terpenoids and aromatic compounds, which show significant biological activities, are isolated from the bryophytes in the past decades. Now the bryophytes have been well known as a source of biologically active, naturally occurring compounds.Bisbibenzyls, a class of characteristic components derived from liverworts, are attracting more and more attention because of their wide range of biological significance. So,Total synthesis and preparation of derivatives of bisbibenzyls with excellent activity is a good way to develop novel drug. Due to the highly strained cyclic structures, some bisbibenzyls show optical activity. It is important to perform studies on the bisbibenzyl stereochemistry for understanding their biosynthesis and mechanism of pharmacological action.In this paper, the liverworts Reboulia hemisphaerica, Heteroscyphus planus, Pallavicinia ambigua and Herbertus aduncus collected in Guizhou Province were phytochemically investigated. A total of 78 compounds were obtained and determined on the basis of extensive spectroscopic means, which were characterized as 15 sesquiterniods,13 bisbibenzyls,27 diterpenoids, and 9 glucosides and so on.20 compounds were new secondary metabolites. Bisbibenzyls exhibited moderate cytotoxic activities. Total synthesis and preparation of derivatives for with excellent activity were developed.37 compounds were isolated from R. hemisphaerica, including 4 new ones, 2-(3,4-Dihydroxyphenyl)ethyl-O-α-L-rhamnopyranosyl-(1→2)-O-β-D-glucopyranosi de (31),2-(3,4-Dihydroxyphenyl)ethyl-O-β-D-xylopyranosyl-(1→2)-O-β-D-allopyranoside (32),2-(3,4-Dihydroxy phenyl)ethyl-O-β-D-xylopyranosyl-(1→2)-O-β-D-glucopyranoside (35) andα,β-Dihydrostilbene-2,3',4',5-tetraol 2,5-di(β-D-glucopyranoside (36). Among of them, bisbibenzyls showed moderate cytotoxic activities.Fifteen compounds were isolated from H. planus, including 11 new ones, Heteroscyphol A-F (40-45), 1α,3β-acetoxy-2β-O-phenylpropionyl-ent-maalian-4β-ol (46), 1α,3β-acetoxy-2β-O-cinnamyl-ent-maalian-4p-ol (47), 1α,3β-acetoxy-2β-O-cis-cinnamyl-ent-maalian-4β-ol (48), ent-maanlian-1α,2β,3β,4β-tetrol (49), (R)-(-)-Heteroscyphide (50). Among of them, (R)-(-)-Heteroscyphide (50) is a new skeleton compound.Eight new labdanne-type diterpenoids (53-57,61-63) were isolated from P. ambigua, together with previously Four known ones.One new bisbebenzyls was isolated from H. aduncus, together with 4 known compounds.The absolute stereochemistry of macrocyclic bisbibenzyls isoriccardin C was investigated through HPLC-CD and computational methods. The absolute configurations of these semistable atropisomers were assigned as M-riccardin D and P-riccardin D using a combination of electronic circular dichroism (ECD).The macrocyclic bisbibenzyl isoriccardin C, which showd cytotoxic activities good, was synthesized. At the same time,8 mannich derivatives and 2 bromo-bisbibenzyls were prepared, which exhibited higher cytotoxic reactivities.