Chemical Constituents Of Four Liverworts And Their Biological Activities

The bryophytes,which comprise more than 18,000 species worldwide,are taxonomically placed between algea and pteridophytes.Collectively,they represent several quite separate evolutionary lines and are classified into three coordinate phyla: mosses,liverworts,and hornworts.Generally,bryophytes are not damaged by bacteria, fungi,insects,snails,and slugs.A number of bryophytes have been used as medicinal plants in North America,China,and Europe.Approximately 90%of liverworts possess cellular oil bodies that are composed of various types of lipophilic terpenoids and aromatic compounds which show significant biological activities.In this paper,the liverworts Marchantia polymorpha and Asterella angusta collected in Sichun Province,Jungermannia atrobrunnea collectd in Zhejiang Province,and Schistochila aligera collected in Hainan Province,were phytochemically investigated.A total of 64 compounds were obtained and 62 of them were determined on the basis of extensive spectroscopic means,chemical transformations,or single-crystal X-ray crystallographic analysis,which were characterized as 21 bisbibenzyls,14 diterpenoids,9 glucosides and so on.26 compounds were new secondary metabolites.Bisbibenzyls exhibited moderate antifungal activity against Candida albicans.From the water-soluble fraction of the ethanolic extract of the liverwort Marchantia polymorpha,16 compounds including one bibenzyl glycoside:α,α′-dihydro-4′-hydroxystilbene 2,5-di-O-β-D-glucopyranoside(1);one shikimic acid glycoside:shikimic acid 4-O-β-D-xylopyranoside(2);and four phenylethanoid glycosides:2-(3,4-dihydroxy-phenyl)ethyl-O-α-L-rhamnopyranosyl-(1″→2′)-O-β-D-allopyranoside (3),2-(3,4-dihydroxy-phenyl)ethyl-O-β-D-xylopyranosyl-(1″→6′)-O-β-D-allopyranoside (4),2-(3,4-dihydroxy-phenyl)ethyl-O-β-D-xylopyranosyl-(1″→6′) -O-β-D-glucopyranoside(5),and 2-(3,4-di-hydroxyphenyl)ethyl-O-β-mannopyranosyl-(1″→3′)-O-α-L-fucopyranoside (6)were isolated.The isolated phenylethanoid glycosides showed strong free radical scavenging effects against DPPH with IC₅₀ values ranging from 10 p.M/ml to 15μM/ml.Bioactivity-guided separation of the ether extract of the liverwort Asterella angusta afforded eight novel bisbibenzyls,asterelin A(17),asterelin B(18), angustatin A(19),riccardin I(20),7'(S)-hydroxyriccardin C(23a and 23b)(two atropisomers),11-O-demethyl marchantin I(21),and dihydroptychantol A(22). Asterelins A and B were the first examples of bisbibenzyls incorporating a novel dibenzofuran link.The antifungal activity of these isolated bisbihenzyls against the common clinical pathogenic fungus Candida albicans was evaluated by both the TLC bioautographic assay and the broth microdilution method.They showed minimal inhibitory concentration(MIC)values ranging from 16 to 512μg/ml.Three new rearranged kaurane-type diterpenoids,jungermatrobrunin A-C(44-46), and eig(?)t new ent-kaurane-type diterpenoids,12β-hydroxy-la,6α-diacetoxy-ent-kaura-9 (11),16-dien-15-one(47),1α,12β-dihydroxy-6α-acetoxy-ent-kaura-9(11),16-dien-15-one (48),1α,6α-diacetoxy-ent-kaura-9(11),16-dien-12,15-dione(49),16R-1a, 6β-diacetoxy-ent-9(11)-kauren-12,15-dione(50),6α,15β-diacetoxy-ent-kaura-9 (11),16-diene(51),6α-hydroxy- 15β-acetoxy-ent-kaura-9(11),16-diene(52),6α,15β-diacetoxy-ent-kaura-9 (11),16-dien-12-one(53),and 12β-hydroperoxy-6α,15β-diacetoxy-ent-kaura-9,(11),16-dien-12-one(54)have been isolated from the liverwort Jungermannia atrobrunnea.Their structures were determined by extensive NMR techniques and X-ray crystallographic analysis.The absolute configurations of these compounds were clarified by CD spectroscopic studies.Jungermatrobrunin A is the first example of an ent-kaurane diterpenoid with a peroxide bridge in the molecule. All of the isolates ent-kaurane-type diterpenoids showed weak antifungal activity against C.albicans. From the ether extract of the liverwort Schistochila aligera,7 compounds were isolated and 5 of them were determined by extensive NMR techniques.Aligeralin A (55),a fusicoccane-type diterpenoid,is a new compound.