- 學位論文
台灣荖藤莖部、菲律賓胡椒莖部及枯里珍根部之化學成分與生物活性之研究
Studies on the Chemical Constituents and Biological Activities from the Stem of Piper taiwanense, the Stem of P. philippinum and the Root of Antidesma pentandrum var. barbatum
摘要
對台灣產植物進行一系列之抗血小板凝集篩選，發現胡椒科之台灣荖藤(Piper taiwanense Lin & Lu)與菲律賓胡椒(P. philippinum Miq.)的甲醇抽出物，對抗血小板凝集具有顯著活性，因而進行此兩種植物化學成分及抗血小板凝集活性之研究。另外經由國家衛生研究院(NHRI)高速藥物篩選中心對台灣產植物進行人類癌細胞株之細胞毒殺篩選，發現大戟科之枯里珍(Antidesma pentandrum Merr. var. barbatum (Presl) Merr.)具有毒殺作用，故對其化學成分及細胞毒性進行研究。 由台灣荖藤莖部分離得到4個新生物鹼：piperolactam E、taiwanamides A－C以及25個已知化合物。而其抗血小板凝集活性化合物分別為4-allylcatechol、eugenol、trans-caffeicaldehyde、piperolactam B、piperolactam C、piperolactam E、2-hydroxy-1-methoxy-4H-dibenzo-[de,g]quinoline-4,5-(6H)-dione、1-cinnamoyl- pyrrolidine、1-(m-methoxycinnamoyl)pyrrolidine、taiwanamides A－C。而4-allylcatechol為主要活性化合物。為了探討其SAR關係，因此製備一系列的1,2-disubstituted 4-allylbenzene化合物，結果發現1,2-diacetoxy-4-allylbenzene與eugenol acetate的活性為4-allylcatechol的3倍強。 由菲律賓胡椒莖部分離得到8個新化合物：(+)-bornyl caffeate、piperphilippinins I－VI、philippinamide以及26個已知化合物。其抗血小板凝集活性測試正在進行中。 由枯里珍根部分離得到13個新化合物：antidesmanins A－F、barbatins A－D、antidesmol、antidesnone、antidesnol以及包括sodium aristolochate-I、aristolochic acid I methyl ester 在內的12個已知化合物。antidesmanins A－D為首次發現具有1,1-dimethylallyl取代基coumarinolignan骨架的化合物。馬兜鈴酸類化合物首次由非馬兜鈴科植物分離出。而其具細胞毒活性化合物為antidesmanins A－C、N-trans-feruloyltyramine與N-trans-feruloyloctopamine。 在這次研究中，由這三種植物中共發現25個新化合物。這些植物的生物活性首次被研究。1,2-disubstituted 4-allylbenzene化合物結構與抗血小板凝集活性的關係已經建立。
並列摘要
As a series of studies on the chemical constituents and biological activities of Formosan plants, the methanolic extract of Piper taiwanense Lin & Lu and P. philippinum Miq. (Piperaceae) showed more potent inhibitory activity on platelet aggregation in vitro. The methanolic extract of Antidesma pentandrum Merr. var. barbatum (Presl) Merr. (Euphorbiaceae) showed significant cytotoxicity against three human tumor cell lines on high-throughput screening by NHRI. Subsequent investigation of the stem extract of P. taiwanense led to the isolation of 4 new alkaloids, piperolactam E, taiwanamides A－C together with twenty-five known compounds. Among them, 4-allylcatechol, eugenol, trans-caffeicaldehyde, piperolactam B, piperolactam C, piperolactam E, 2-hydroxy-1-methoxy-4H-dibenzo-[de,g]quinoline- 4,5-(6H)-dione, 1-cinnamoylpyrrolidine, 1-(m-methoxycinnamoyl)pyrrolidine, and taiwanamides A－C as the active principles with anti-platelet aggregation in vitro. 4-Allylcatechol was the major active compound. For establishing the SAR, 1,2-disubstituted 4-allylbenzene derivatives were prepared and the activities of 1,2-diacetoxy-4-allylbenzene and eugenol acetate were 3 fold stronger than 4-allylcatechol. Investigation of the stem extract of P. philippinum led to the isolation of eight new compounds, (+)-bornyl caffeate, piperphilippinins I－VI and philippinamide together with 26 known compounds. Anti-platelet aggregation tests are under progress. Subsequent investigation of the root extract of Antidesma pentandrum var. barbatum led to the isolation of 13 new compounds, antidesmanins A－F, barbatins A－D, antidesmol, antidesnone and antidesnol together with 12 known compounds including sodium aristolochate-I and aristolochic acid I methyl ester. 1,1-Dimethylallyl substituent in the coumarinolignan moiety like antidesmanins A－D were first found in nature. Aristolochic acid analogoues were first isolated from Euphorbiaceae besides Aristolochiaceae. Antidesmanins A－C, N-trans-feruloyltyramine and N-trans-feruloyloctopamine showed cytotoxic activities. In this study, we have isolated 25 new compounds from these three plants. The biological activities of these plants were first studied. The SAR of 1,2-disubstituted 4-allylbenzene derivatives in anti-platelet aggregation activity was established.