方俊民Fang, Jim-Min臺灣大學:化學研究所陳志安Chen, Chih-AnChih-AnChen2010-06-302018-07-102010-06-302018-07-102008U0001-2907200816280300http://ntur.lib.ntu.edu.tw//handle/246246/187451視網膜色素上皮細胞層 (retinal pigment epithelium, RPE) 位於眼睛的後方，厚度只有一層，排列在布魯赫氏膜與光接受器之間。RPE功能眾多，主要有光線吸收、維生素A的儲存與運送、供給感光細胞氧氣和養份，及沉澱廢物的清除。RPE會隨著年齡的增加而死亡或游離至他處，RPE功能退化會引發一些視網膜疾病，常見的有，增殖性視網膜病變 (proliferative vitreoretinopathy)， 糖尿病所引發的視網膜血管新生 (proliferative diabetic retinopathy)，老年性黃斑部病變 (aged-macular degeneration, AMD)等，都與RPE細胞的機能息息相關。斛為蘭科植物，是重要的常用中藥，霍山石斛 (Dendrobium huoshanense) 為石斛種類中之上品，原產於中國安徽霍山等地，與靈芝、冬蟲夏草並列為中國三大珍貴靈草。根據古方與相關研究報告，石斛藥用廣泛，除了具有「清肝明目」療效，也有抗衰老、抗腫瘤、治療白內障、提高身體免疫力的功能。霍山石斛中分離出活性小分子—芹菜素配醣體具有「明目」療效，我們希望藉由化學合成方法來彌補霍山石斛天然物資源的缺乏，合成一系列芹菜素衍生物，搭配生物活性分析，篩選出最佳的活性分子，進而推測其藥效基團，並探討結構A variety of C-glycosylflavonoids are found widely distributed in the plant kingdom. Dendrobium huoshanense is a well-known traditional Chinese medicine. Apigenin 6,8-di-C-glycosides have been suggested to exist in D. huoshanense to exhibit an activity for eye protection. Because the structure of the chemical constituent and the biological mechanism were unclear, we aim to synthesize a series of apigenin 6,8-di-C-glycosides and analogues for the structure–activity relationship study. key reaction was carried out by using Sc(OTf)3 as the promoter to furnish the C-glycosylation on phloroacetophenone with unprotected saccharides. The key compound was further converted to mono- and di-C-glycosides of apigenin. In order to increase the diversity, different sugars (D-glucose, L-arabinose, D-xylose etc.), and phenols were used to synthesize the analogues.誌謝......................................................I文摘要................................................III英文摘要.................................................IV錄......................................................V目錄..................................................VII程目錄.................................................IX目錄....................................................X稱用語對照表...........................................XI一章 緒論..............................................1一節 RPE 細胞的介紹....................................11-1.1 老年性黃斑部病變..................................11-1.2 自由基對RPE細胞的氧化傷害.........................3二節 霍山石斛..........................................4三節 黃酮類化合物......................................51-3.1 黃酮類對於RPE細胞抗氧化功能.......................81-3.2 黃酮類對於RPE細胞抵抗A2E光氧化作用................9四節...................................................111-4.1 類黃酮配醣體.....................................111-4.2 醣化作用.........................................14二章 結果與討論.......................................19一節 apigenin 6,8-di-C-glycoside合成方法探討..........192-1.1 逆合成分析.......................................202-1.2 合成apigenin 6,8-di-C-glycoside..................202-1.3 選擇性在apiginin的6, 8位置接上不同單醣...........222-1.4 改善apigenin 6,8-di-C¬-glycosides之合成..........25二節 Sc(OTf)3 催化做醣化反應..........................272-2.1 使用未保護的醣類做快速C-glycosylation.............272-2.2 使用未保護的醣類合成6,8-di-C-glycosyl flavones....282-2.3 解析6,8-di-β-C-glycosyl flavones之結構............31三節 Assay Result.....................................322-3.1 Antioxidation assay for RPE cell..................332-3.2 Previous antioxidation assay for RPE cell results...........................................38四節 結論..............................................41三章 實驗部分.........................................43四章 參考文獻.........................................77錄： 1H and 13C 光譜...................................854534195 bytesapplication/pdfen-US視網膜色素上皮細胞類黃酮抗氧化Retinal Pigment Epithelial CellsFlavonoidAntioxidantsthesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/187451/1/ntu-97-R95223039-1.pdf