Studies On Chemical Constituents And Synthesis Of Derivatives And Biological Evaluation Of Artocarpus Altilis

Artocarpus altilis (Parkinson) Fosberg, an exceptionally rich source of flavonoids, is native to South East Asia, New Guinea, and South Pacific Ocean Island. It has been used traditionally in Taiwan and Indonesia for the treatment of hypertension, diabetes, asthma, fever, and liver cirrhosis. The chemical constituents of the leaves of A. altilis which were collected in september 2004 from Bandung (Indonesia), were investigated using in vitro anti-atherosclerotic cell model guided fractionation. As a result, 23 compounds were isolated by means of a series of normal and reversed-phase, Sephadex LH-20 chromatography. Among these compounds, eight compounds are new geranyl flavonoids, and the other three compounds are first obtained from A. altilis. Structures of all the compounds were elucidated by ID NMR, 2D NMR, ESI-MS, HR-ESI-MS, UV, IR, Optical rotations spectral analysis and by comparison with published values. Some new compounds were evaluated for their in vitro cytotoxicity against a small panel of human cancer cells. Compound Aa 4 was the most potent against the human lung adenocarcinoma cells and human colon carcinoma cells. At the same time, the tested compounds hadα-glucosidase inhibitory activities.Aa 3 and Aa 5-1 which were isolated as major component, were modified in two approaches including etherification and esteration. As a result, 32 compounds were synthesized including 31 new compounds. The Claisen rearrangement had been tried for the synthesis of the C-prenyl derivatives of Aa 3 from the O-prenyl derivatives of Aa 3. During the experiment, two intramolecular eyclized derivatives were synthesized unexpectantly. The Friedel-Crafts reaction confirmed that the low electricity density of ring A of dihydrochalcone prevented the Claisen rearrangement. The etherification and esteration derivatives showed little cytotoxicity against the human cancer cells at 80μM. The results indicated that hydroxyl group played an important role in the cytotoxicity assay.The total flavonoid of A. altilis was prepared by macroporous resin chromatography.The mixture of the total flavonoid andβ-sitosterol was evaluated their anticardiovascular diseases activities in vivo. The results indicated that the mixture, with low toxicity, could inhibit ADP induced platelet aggregation, decrease blood viscosity, protect the acute myocardial ischemia injury in SD rats induced by Pituitrin. All the results suggested that the mixture has the potency against cardiovascular diseases.