- 學位論文
小西氏楠葉部成分、野薑花根莖成分及coronarin D衍生物製備之研究
Chemical investigation of Machilus konishii leaves and Hedychium coronarium rhizomes and preparation of coronarin D derivatives
若您是本文的作者，可授權文章由華藝線上圖書館中協助推廣。
摘要
本論文包括三個部分： 第一部分 小西氏楠葉部成分之研究 小西氏楠Machilus konishii (Hayata)為樟科楨楠屬的植物，中型至大型常綠喬木，為台灣特有，分佈於臺灣中南部中低海拔的闊葉林區。α-Glucosidase抑制劑為臨床上一類口服降血糖藥物，用於治療第二型糖尿病，主要作用為抑制碳水化合物在腸道的消化吸收。本研究以抑制α-glucosidase活性為導向，利用Sephadex LH-20管柱、離心分配層析、矽膠管柱、低壓逆相層析管柱以及半製備高壓液相層析管柱進行分離，自小西氏楠葉部乙醇萃取物分離並鑑定出二十九個化合物，分別屬於黃酮類(1, 7-25)、epicatechin聚合體類(2-6)、木脂素類(26-27)和酯類(28-29)。其中，化合物6為首次自天然物中分離得到，而化合物20、22、23及27為新化合物。活性測試結果顯示，化合物cinnamtannin B-1 (4)、kaempferol 3-O-(2-β-D-apiofuranosyl)-α-L-rhamnopyranoside (16)、tiliroside (24)和kaempferol 3-O-α-L-(2",4"-di-E-p-coumaroyl)-rhamnopyranoside (25)之IC50分別為24.2 μM、30.3 μM、18.3 μM和23.1 μM。 第二部分 野薑花之根莖部成分研究 野薑花Hedychium coronarium Koenig又稱為穗花山奈，為薑科蝴蝶薑屬的植物，分佈於印度、馬來西亞、越南、中國大陸南方和台灣，生長於低海拔的濕地。文獻報導其根莖部含有大量coronarin D，為具細胞毒性的雙萜類化合物，本研究擬分離大量此化合物，以供第三部分化學修飾研究用。野薑花根莖乙醇萃取物以極性劃分為氯仿、正丁醇和水可溶部分後，氯仿可溶部分進一步以乙腈和己烷進 行極性劃分成乙腈和己烷可溶部分，其中乙腈可溶部分以矽膠管柱分離可得到大量的coronarin D (30)成分。而正丁醇可溶部分則經Sephadex LH-20管柱、離心分配層析、矽膠管柱、低壓逆相層析管柱以及半製備高壓液相層析管柱進行分離，鑑定出十三個化合物，分別屬於diaryheptanoids (31-37)、芳香環配糖體(38-40)和核苷類(41-43)，其中化合物31-37為新天然物，其結構係由光譜分析及化學反應而確定。 第三部分 Coronarin D衍生物之製備 本研究擬以coronarin D (30)作為起始物，以一系列反應，利用原有內脂環，開環再進一步重新形成七員環，合成12,13-dihydrogalanal A/B，或進一步胺基化形成胺基衍生物。針對exo-methylene修飾成羥甲基與提高反應性的步驟方面，嘗試了包括硼氫化-氧化反應、形成epoxide和與二氧化硒反應引入酮基等許多方法，可惜在產率方面都偏低，以致無法順利得到七員環之標的產物。然過程中一些較為成功的反應方法，仍可以作為未來繼續研究之碁石，包括以硫酸二甲酯/碳酸鉀進行甲基化反應，可針對內脂環進行開環形成methyl ester；以NiCl2•6H2O和硼氫化鈉在甲醇中反應，產生(Ni2B)2H3，可選擇性還原Δ12位置上的共軛雙鍵，而不影響Δ8位置上的exo-methylene；以pyridinium chlorochromate作為氧化劑，可氧化15位置上屬於hemiacetal上的羥基，形成酸酐結構；以硼氫化鈉進行還原，再以濃硫酸和少量甲醇進行合環，兩階段反應可選擇性還原15位置上屬於hemiacetal上的羥基。
並列摘要
This dissertation includes three parts: Part 1. Chemical investigation of the leaves of Machilus konishii Machilus konishii Hayata (Lauraceae) is a medium-sized evergreen tree, endemically distributed in the broadleaved forests from low to medium altitudes in the central to southern parts of Taiwan. α-Glucosidase inhibitors, a class of orally administered hypoglycemic agents for type 2 diabetes, can decrease the absorption of carbohydrates from the intentine. Bioassay-guided fractionation against α-glucosidase has resulted in isolation and characterization of 29 compounds from the EtOH extract of the leaves of Machilus konishii by repeated chromatography on Sephadex LH-20, silica gel, Lobar RP-18, semipreparative HPLC, and centrifugal partition chromatography. These compounds were characterized as flavonoids (1, 7-25), epicatechin oligomers (2-6), lignans (26, 27), and esters (28, 29). Compound 6 is the first occurrence as natural product, and compounds 20, 22, 23 and 27 are new compounds. Cinnamtannin B-1 (4), kaempferol 3-O-(2-β-D-apiofuranosyl)-α-L-rhamnopyranoside (16), tiliroside (24), and kaempferol 3-O-α-L-(2",4"-di-E-p-coumaroyl)-rhamnopyranoside (25) showed moderate inhibitory activity against α-glucosidase with the IC50 values of 24.2 μM, 30.3 μM, 18.3 μM and 23.1 μM, respectively. Part 2. Chemical investigation of Hedychium coronarium rhizome Hedychium coronarium Koenig (Zingiberaceae) is a 1−3 m tall herb, distributed in wetlands at low elevations of India, Malaysia, Vietnam, southern China, and Taiwan. Several cytotoxic compounds have been identified from the rhizome of this plant. To supply some of these active ingredients for chemical modification and to disclose polar constituents, the constituents of this part were reinvestigated. The EtOH extract were divided to fractions soluble in CHCl3, n-BuOH, and H2O. The CHCl3-soluble fraction was further partitioned into hexanes- and MeCN-soluble parts. The major component, coronarin D (30), was isolated from MeCN-soluble fraction by silica gel column chromatography and 13 compounds were isolated from n-BuOH -soluble fraction by repeated chromatography on Sephadex LH-20, silica gel, Lobar RP-18, semipreparative HPLC, and centrifugal partition chromatography. These compounds were characterized as diaryheptanoids (31-37), aromatic glycosides (38-40), and nucleosides (41-43). Of them, compounds 31-37 are new compounds. Their structures were established by spectroscopic analysis and chemical method. Part 3. Preparation of coronarin D derivatives The aim of this study is to prepare 12,13-dihydrogalanal A/B or their amine derivatives from coranarin D (30). After some attempts, our work was impeded by modification of exo-methylene to a hydroxymethyl group and failed to get cyclized target products. However, some successful methods could be helpful to the future study. Reaction with dimethyl sulfate/potassium carbonate could open the lactone ring besides forming methyl ester. Reaction with NiCl2•6H2O and NaBH4 could selectively reduce the Δ12 conjugated doube bond without affectimg the exo-methylene (Δ8(17)). Oxidation of hemiacetal hydroxy group at C-15 with pyridinium chlorochromate could yield anhydride. Selective reduction of hemiacetal hydroxy group at C-15 could be achieved by NaBH4 and then cyclized by conc. H2SO4 in MeOH.
參考文獻
2. Lin, H.C. & Lee, S.S. Proanthocyanidins from the leaves of Machilus philippinensis. Journal of Natural Products 73, 1375-1380 (2010).
3. Lin, H.C., Tsai, S.F. & Lee, S.S. Flavonoid glycosides from the Leaves of Machilus philippinensis. Journal of the Chinese Chemical Society Taipei 58, 555-562 (2011).
4. Lee, S.S., Lin, Y.S. & Chen, C.K. Three adducts of butenolide and apigenin glycoside from the leaves of Machilus japonica. Journal of Natural Products 72, 1249-1252 (2009).
6. Lu, S.T. Studies on the alkaloids of Formosan Lauraceous plants. II Alkaloids of Machilus Kusanoi Hayata. (2). The isolation of dl-Coclaurine. Journal of the pharmaceutical society of Japan 83, 19-21 (1963).
7. Tomita, M., Lu, S.T. & Lan, P.K. Studies on the alkaloids of Formosan Lauraceous plants. IV Alkaloids of the several Machilus genus plants. Journal of the pharmaceutical society of Japan 85, 588-593 (1965).