Chemical Constituents Of Six Liverworts,Total Synthesis Of Plagiochin G And Their Biological Activities

Bryophytes are taxonomically placed between the algae and the pteridophytes. Morphologically, they are divided into three classes, liverworts (Hepaticae), mosses (Musci) and hornworts (Anthocerotae). There are more than6000liverworts in the world, about880species of which have been found in China. Among the bryophytes, liverworts have been phytochemically investigated in the most detail, because they possess appealing cellular oil bodies, which are characteristic, membrane-bound cell organelles consisting of ethereal terpenoids and aromatic compounds, while the other two phyla do not. Many of the isolated compounds from liverworts exhibit interesting biological activities. Lots of different types of compounds are isolated from liverworts in the past decades. Now liverworts have been well known as a good source of biologically active comounds.Bisbibenzyls, a class of characteristic compounents isolated from liverworts, become to be a synthsis targeting recently because of their wide range of biological significance. So, total syntheses and preparation of bisbibenzyls with excellent biological activities is a good way to develop novel drugs.In this research, the liverworts Chandonanthus birmensis, Scapania stephanii and Cephaloziella kiaeri collected from Guangxi Zhuang Autonomous Region, and Frullania serrata collected from Yunnan Province, as well as Porella acutifolia subsp. tosana and Plagiochila vexans collected from Guizhou Province, were phytochemically investigated. A total of61compounds, including39diterpenoids,10sesquiterpenoids,2triterpenoids,6steriods, and4bibenzyls, were isolated and identified on the basis of NMR, MS, single crystal X-ray diffraction analysis, CD exciton chirality method and time-dependent density functional theory (TDDFT) CD calculations.28of them were new compounds, containing25new diterpenoids and3new sesquiterpenoids. Cembrane-type diterpenoids isolated from the liverwort C. birmensis exhibited weak cytotoxic activity. cis-Clerodane-type diterpenoids isolated from S. stephanii showed significant plant growth inhibitory activity. This work represents the first phytochemical investigations on the plants of C. birmensis, S. stephanii and C.kiaeri.Separation of the liverwort C. birmensis afforded seven diterpenoids, including six cembrane-type diterpenoids, named chandonanones B (1), C (2), E (3) and F (4), chandonanthone (5), and isochandonanthone (6), and one dolabellane-type diterpenoid2,10,14-triacetoxy-7,8,18,19-diepoxydolabell-3(E)-ene (7). The cytotoxicities of compounds1-7were tested against the human lung carcinoma cell lines NCI-H292and NCI-H1299and rat pheochromocytoma cell line PC12using the MTT method with IC50values ranging from19.5to48.7μM.From the liverwort S. stephanii, twelve c/s-clerodane-type diterpenoids, including stephanialides A-E (8-12), scaparvins A-C (13-15), parvitexins B (16) and C (17),3-chloro-4-hydroxy-parvitexin A (18), as well as scapanialide B (19), were isolated. The plant growth inhibitory activities of six compounds (10,12-14,16and17) were tested with models of the seeds of A. thaliana (Thale cress, Brassicaceae), L. sativum (garden cress, Brassicaceae) and B. pekinensis (Chinese cabbage, Brassicaceae). All six compounds could significantly inhibit root elongation of seeds of these three species with IC50values ranging from3.5to30.7μg/mL.Twenty one compounds, including eighteen c/s-clerodane diterpenoids, named cephaloziellins A-P (20-35), amphiacrolide F (36) and cephaloziellin Q (37), as well as three sesquiterpenes, named4β,6β-dihydroxy-1α,5β(H)-guai-9-ene (38), teucladiol (39) and ent-3β-hydroxyspathulenol (40), were isolated from the liverwort C. kiaeri. Sixteen cis-clerodane diterpenoids (20-35) were new compounds.Two new cadiane-type sesquiterpenes, named frullanic acid (41) and frullanic acid methyl ester (42), and four known bibenzyls, named brittonin B (43),3,3’-dimethoxy-4,5-methylene-dioxybibenzyl (44),3,4,5,3’,4’-penla-methoxy-bibenzyl (45), and (±)-3-(4’-methoxy-benzyl)-5,6-dimethoxyphtbalide (46), were isolated from the liverwort F. serrata.One new sesquiterpenoid, named guaian-3-en-2a,14-6α,12-diolide (47) and six known steriods,(20R)-6-hydroxystigmasta-4,22-dien-3-one (48),(20R)-3-hydroxystigmasta-5,22-dien-7-one (49),7-oxositosterol (50),(24S)-ethyl-5,22-cholestadien-3(51), ergosterol peroxide (52), and β-sitosterol (53), were isolated from the liverwort P. acutifolia subsp. tosana.From the liverwort P. vexans, three known aromandane-type sesquiterpenes, named aromadendrane-4α,10α-diol (54), aromadendrane-4β,10β-diol (55), and aromadendrane-4a,10β-diol (56), one known seco-aromandane-type sesquiterpene ent-2,3-secoalloaromadendra-4(14),10(15)-diene-2,3-diol (57), two known fusicoccane-type diterpenoids, named fusicoauritone (58) and anadensin (59), as well as two known triterpenoids, named betulinic acid (60) and oleanolic acid (61), were isolated.Plagiochin G with excenlent cancer chemopreventive activity have been synthsised. Four of its ester derivatives have been prepared. All of them showed good cancer chemopreventive activity.