Studies On The Chemical Constituents And Their Cytotoxicity Of Agathis Macrophylla

The genus Agathis belongs to the widely distributed Araucariaceae family and consists of about 20 species all over the world, which are mainly distributed in the tropical zone such as Philippine, Viet Nam, Malay Peninsula and Australia. There is only a species, Agathis macrophylla, in China, which was introduced and used for garden trees, timbers, furniture. Its resin was used for industrial and medical purpose. Some species in this genus have been traditionally applied for many medical purposes, including relieving internal heat, antibiotic, reducing phlegm and cough, invigorating the circulation and diuresis. The plant was collected in Jianfengling National Forest Park, about 1000 m high above sea level, Hainan Province.In order to explore more plants with medical value in the genus Agathis, and develop the new herbal plant resources in China, we carried out systematic phytochemical studies on the aerial part of A. macrophylla. This is the first time to report the pytochemical study on it. From the 95% ethanol extract of the aerial part, 40 compounds were isolated by means of silica gel, preparative thin layer chromatography, RP C-18, Sephadex LH-20, Diaion HP-20, MCI gel column chromatography, etc. The structures of the 40 compounds were elucidated by spectroscopic method (IR, MS, UV,1H NMR,13C NMR, DEPT, NOSEY, 'H-'HCOSY, HMBC, HMQC), in combination with comparison to the literature data or authentic samples. They were 14 diterpenoids,5 flavonoids,8 sterols and triterpenoids,5 sesquiterpene and ionones derivatives, and the others. Among which, 6 new compounds were elucidated as methyl (4S,9S)-19-hydroxy-15,16-dinor-labda-8(17), 11E-dien-13-oxo-18-oate (Am1), (4R,9R,13S)-13-hydroxypodocarp-8(14)-en-19-oic acid (Am2), (4R,9R,13R)-13-hydroxyl-podocarp-8(14)-en-19-oic acid (Am3),3β,23α-dihy-droxyergost-5-en-7-one (Am23), (2R,3R,9R)-trihydroxy-megastigman-5-en-9-O-β-D-glucopyranoside(Am29), glcp-β(1'→1)-3-deoxy-4α,5α- dihydroxy-2-oxo-(2,6)-pyranheptose (Am35). The absolute configuration of novel diterpenoids Am1 and Am2 with novel structure was established by CD spectra. The absolute configuration of Am23 was elucidated by the acid hydrolysis and the determination of suger. Compounds Aml-Am7 and Am9-Am14 were evaluated for cytotoxicity against promyelocytic human leukemia HL60 cell and SMMC-7721 hepatocarcinoma cell.Finally, the different kinds of biflavonoids from 1978 to 2010 were reviewed in the thesis.The results of this thesis would contribute to the research on the chemical constituents of A. macrophylla and supply scientific evidences for searching new natural medicines. This study may also help utilize and develop the natural resources of our country.