台灣產鐘萼木根部之成分研究

Abstract

本論文主要研究鐘萼木（Bretshneidera sinensis Hemsley）根部含有之天然物活性成分，植物採自於台灣新北市瑞芳山區，將其根部打碎後使用酒精重複萃取三次，接著將獲得的初萃物以各種管柱色層分析方法進行分離，並利用各項分析儀器鑑定其中所含之化學組成成分，實驗結果共分離了17個化合物，其中包含了1個新的木質酚素(lignan, 1)，屬於diarylbutane type lignan骨架、1個新的含硫生物鹼(sulfur-containing alkaloid, 2)，屬於3-methyl-1,3-benzothiazine-2,4-dione骨架、3個首次於天然物中發現的已知化合物，分別為N-ethyl-6-methoxybenzenemethanamine (3)、O-ethyl-6-methoxybenzyl carbamothioate (4)與4-(methylthiomethyl)phenol (5)，以及12個已知化合物。 分離得到的化合物結構皆利用核磁共振圖譜1D NMR（1H NMR 和 13C NMR）及2D NMR（COSY、HSQC、HMBC、NOESY）進行解析，加上各種物理數據分析，包括熔點、紅外線光譜、紫外線光譜、圓二色性光譜儀及高解析電灑式質譜儀，最後再經由與化學結構資料庫（Reaxys）進行相關文獻比對而得到確認。 最後將所分離得到的化合物分別進行抗發炎、抗氧化以及抗癌細胞的生物活性檢測。其中，化合物5和化合物8分別對HEp-2及MCF-7具有最佳的抗癌細胞活性，其ED50各為10.9和10.2μg/ml。在抗氧化活性方面，化合物8具最佳之抗氧化能力，其ED50為0.93μg/ml；其次為化合物9，其ED50為2.81 μg/ml，而標準品vit E之ED50為13.0μg/ml。

In this thesis, the phytochemical study of the chemical constituents of Bretshneidera sinensis Hemsley was performed. The roots of B. sinensis were extracted with ethanol and the crude extract was separated by using extensive column chromatography. Consequently, seventeen compounds were isolated including two new compounds, three new natural products as well as twelve known compounds. Compound 1 was identified as a new lignan with diarylbutane skeleton, while compound 2 was characterized as a new sulfur-containing alkaloid, which belongs to the skeleton of N-benzyl-S-methyl-thiocarbamate. In addition, three known compounds, N-ethyl-6-methoxybenzenemethanamine (3)、O-ethyl-6-methoxybenzyl carbamothioate (4) and 4-(methylthiomethyl)phenol (5) were obtained from the nature for the first time. All above compounds were elucidated and their structures were established by application of spectroscopic analysis, such as 1D NMR(1H NMR and 13C NMR) as well as 2D NMR(COSY, HSQC, HMBC, NOESY) techniques. In terms of physical methods, melting point, infrared spectroscopy (IR), ultraviolet spectroscopy (UV), circular dichroism (CD) and high resolution electrospray ionization mass spectroscopy (HRESIMS) were applied. Moreover, the structures of all isolated compounds were confirmed precisely by checking through the chemical database, Reaxys. Finally, all the isolated compounds were tested and evaluated for the biological activities, which include anti-inflammatory, anti-oxidation and cytotoxic activities. In this case, compounds 5 and 8 exhibited significant antitumor activities with an ED50 at 10.9 and 10.2μg/ml, respectively. As for anti-oxidative activity, it showed the greatest result for compound 8 (ED50 0.93μg/ml), followed by compound 9 (ED50 2.81μg/ml). The value of standard vitamin E showed ED50 at 13.0μg/ml.