Chemical and Biological Studies on the Constituents of Rollinia mucosa Baill. and the Synthesis of Isoquinoline Derivatives

• Main Authors: Reen-Yen Kuo, 郭荏耘
• Other Authors: Yang-Chang Wu
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/84767661870035281015

博士 === 高雄醫學大學 === 藥學研究所 === 91 === In the continuing research of Formosan Annonaceous plants, the methanolic extracts of leaves and stems of Rollinia mucosa Baill. were investigated for their chemical constituents and biological activities, respectively. Fifty-one compounds were isolated including twenty-eight alkaloids, three flavonoids, six lignans, five steroids, one acetogenin, one pyrrole, and seven benzenoids. Among these compounds, eight of them including (-)-artabonatine A (AP-10), romucosine A-D (AP-13~16), promucosine (PA-2), rollipyrrole (PY-1) and romucosine I (PH-1) are isolated as new compounds, and twenty-eight of them were firstly derived from this species. The aporphine possessed N-methoxycarbonyl moiety such as romucosine A-D (AP-13~16), was selected as the target for the further total synthesis study. Sixty-one compounds were synthesized, including eleven amides (AMS-1~11), nine pyrrolo-benzylisoquinolines (PB-1~9), thirty-six benzylisoquinolines(BS-1~8, BS-9a~17a, BS-9b~17b, BS-9c~17c, BS-17d) , two indoloisoquinolines (IN-1~2), and three target N-methoxycarbonylaporphine (AP-17, 20, 21). The new synthesis approach of aporphines using palladium as ring closure reagent was never reported. Four natural occurred aporphines and a benzylisoquinoline were treated with active charcoal to give dehydrogegated derivatives via auto-oxidation. The semisynthesis using active charcoal as dehydrogenation agent is not only efficient but also mild and economic. Several compounds were screened for their cytotoxicity, antiplatelet activity, and -adrenoreceptor affinitiy. From these screenings, the SAR of antipletelet activity of benzylisoquinolines (BS-9a~17a, BS-9b~17b, BS-9c~17c, BS-17d) and pyrrolo- benzylisoquinolines (PB-1~9) were established. The most potent compound, PB-9, which strongly against PAF induced aggregation, was studied for its mechanism of action. The preliminary pharmacological study has showed the compound obviously reduced the phosphodiesterase activity and therefore induced the platelet aggregation.