本論文包含兩個部分，這兩個部的主旨皆為藥物合成，分別為 Arcyriaflavin A 衍生物與白藜蘆醇衍生物之合成，已有文獻證實上述的兩種結構具有諸多生物活性，可應用於各種醫學上的治療，小至保養品，大至退化性疾病藥物，其中抗癌的醫療效果最受重視。
第一部分為 Arcyriaflavin A 衍生物之合成，主要目的為設計出 Arcyriaflavin A 相關衍生物可通用的合成路徑。合成方法為利用 2,3-二溴馬來亞醯胺 (2,3-Dibromomaleimide) 與苯環上有不同取代基之吲哚格林鈉試劑 (Indole Grignard Reagent) 進行加成取代反應，以合成出多個吲哚黃素類化合物，其中最大的突破為新開發出利用 LED 燈條照光誘導進行自由基環化，此方法相較於傳統利用 2,3-二氯-5,6-二氰對苯醌 (2,3-Dichloro-5,6-dicyano-p-benzoquinone, DDQ) 的氧化合環方法更加安全且方便，在產率上也有更好的成果。不僅如此，利用 DDQ 合環的適用範圍很有限，鹵素取代基之 2,3-二溴馬來亞醯胺作為起始物時無法成功獲得預期產物，然而開發出的新方法成功克服了這項障礙，合成了四種鹵素取代衍生物，接著進一步還原，以分別探討合環及還原產物的生物活性。
第二部分為白藜蘆醇衍生物之合成，因為白藜蘆醇及其衍生物已頻繁的被應用於多種醫療藥品當中，但白藜蘆醇對人體的作用機制還有待商確。本研究期望於白藜蘆醇修飾上胺基，以此作為媒介銜接上化學探針，以便在進行生物實驗時作為觀察依據，探討白藜蘆醇於人體中的運作機制。本論文透過威悌反應 (Wittig Reaction)、溴化反應 (Bromination) 與赫克反應 (Heck reaction) 的合成路徑，經條件優化後，已成功建立出含硝基取代的白藜蘆醇分子，未來希望將分子上的硝基還原為胺基並進行化學探針的修飾，以利後續於生物實驗進行觀察。

This thesis consists of two parts, both of which focus on drug synthesis, namely the synthesis of Arcyriaflavin A derivatives and amino-substituted resveratrol derivatives. In past studies, the above two structures have been proven to possess multiple biological activities. The various medical application ranges, from skin care products to drugs for degenerative diseases, and cancer.
The first part is the synthesis of Arcyriaflavin A derivatives. One of the main purposes is to develop a general synthetic route for the derivatives of Arcyriaflavin A. At present, through reacting 2,3-Dibromomaleimide and indole Grignard reagent with different substituents multiple bisindolylmaleimide analogs could be synthesized, In this thesis, the reaction conditions were further to improve the efficiency of the synthesis rout. A new method for cyclization driven by LED light was developed. This method is safer, more convenient, and better yielding, compared with the traditional oxidative cyclization method using DDQ which also have limited substrate scope However, this new method successfully overcome this problem and four halogen-substituted derivatives have been synthesized. The cyclic products were then further reduced in order to investigate the biological activities of the cyclic and reduction products, respectively.
The second part is the synthesis of resveratrol derivatives. Resveratrol and its derivatives have been frequently used in various medicines, but the mechanism of action of resveratrol in cell remains to be determined. This thesis hope constructs an amino group on resveratrol as a reaction handle to install chemical probes for biological studies. In this thesis, the synthesis of nitro-substituted resveratrol is achieved via Wittig Reaction, bromination and Heck reaction. Finally, the nitro group could be reduced to an amino group complete the target molecule.

論文審定書i
致謝ii
中文摘要iii
Abstract v
目錄vii
圖目錄x
表目錄xii
光譜目錄xiii
縮寫表xvi
第一部份 Arcyriaflavin A 衍生物之合成1
第一章 第一部份之緒論1
1.1 Arcyriaflavin A 的應用簡介1
1.2 Arcyriaflavin A 相關衍生物合成方式介紹7
1.2.1 利用吲哚格林納試劑進行加成取代反應7
1.2.2 利用狄耳士-阿德爾反應 (Diels-Alder reaction) 進行合成8
1.2.3 利用費歇爾吲哚合成 (Fischer indolization) 進行合成路徑設計9
1.2.4 利用鈀 (0) 催化進行環化合成路徑設計10
1.2.5 利用氧化光環化 (Oxidative Photocyclization) 進行合成11
1.3Arcyriaflavin A相關衍生物研究動機與實驗設計12
1.3.1 研究動機12
1.3.2 實驗室過去之合成方法12
第二章 第一部份之實驗結果與討論15
2.1 2,3-二溴馬來醯亞胺甲基化之優化15
2.2 吲哚基馬來醯亞胺衍生物之合成優化16
2.2.1 吲哚基馬來醯亞胺衍生物之合成優化16
2.2.2吲哚基馬來醯亞胺衍生物之優化純化方式19
2.3 吲哚基馬來醯亞胺衍生物之合環反應20
2.3.1 利用 DDQ 自由基合環反應之純化方法20
2.3.2 利用kessil LED 化學燈進行合環反應21
2.3.3 利用 LED 燈條進行照光合環反應21
2.3.4 照光合環反應之優化22
2.3.5 照光合環反應之純化方式25
2.3.6 照光合環反應之反應機制探討26
2.4 Arcyriaflavin A 衍生物之還原反應28
2.5 結論29
第二部份 胺取代白藜蘆醇衍生物之合成30
第三章 第二部分之緒論30
3.1白藜蘆醇的應用簡介30
3.2 白藜蘆醇相關衍生物合成方式介紹31
3.2.1 利用霍納-沃茲沃思-埃蒙斯反應 (Horner–Wadsworth–Emmons reaction, HWE) 進行合成31
3.2.2 利用赫克反應 (Heck reaction) 催化進行合成32
3.2.3 利用 Heck Matsuda coupling 進行合成34
3.3 白藜蘆醇相關衍生物研究動機與實驗設計35
3.3.1 研究動機35
3.3.2 實驗設計36
第四章 第二部分之實驗結果與討論37
4.1 威悌反應修飾官能基37
4.2 溴化反應進行加成38
4.3 赫克反應催化進行合成39
4.4 利用三溴化硼進行脫保護41
4.5 結論41
第五章 參考文獻42
第六章 實驗步驟與光譜數據49
6.1 儀器設備與藥品材料49
6.2 Indolocarbazole derivatives 合成步驟與數據52
6.2.1 化合物 25 之合成52
6.2.2 化合物 26 之合成53
6.2.3 化合物 33 之合成54
6.2.4 化合物 34 之合成56
6.2.5 化合物 35 之合成57
6.2.6 化合物 36 之合成59
6.2.7 化合物 28 之合成60
6.2.8 化合物 37-40 之合成61
6.2.9 化合物 41-42 之合成64
6.2.10 化合物 43 之合成66
6.3 合成白藜蘆醇之步驟與數據68
6.3.1 化合物71 之合成68
6.3.1 化合物 73 之合成69
6.3.1 化合物 70 之合成70
6.3.1 化合物 69 之合成72
第七章 光譜資料74

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