臺灣博碩士論文加值系統

本論文主要合成6-aminouridine 和6-(1,2,4-oxadiazol-3-yl)uridine 兩種類型的衍生物，作為具潛力的 orotidine 5’-monophosphate decarboxylase (ODCase) 的酵素抑制劑。
第一部分以6-cyano-1,3-dimethyluracil 作為反應模型，與一級胺試劑進行取代反應，可得到6-alkylamino-1,3-dimethyluracil 的產物，這個方法應用於6-cyanouridine 的衍生物上，同樣可藉由取代反應得到一系列6-alkylaminouridine 的衍生物。
第二部分將6-cyano-1,3-dimethyluracil 作為起始物與疊氮化鈉進行 click 合環反應，可得到6-(tetrazol-5-yl)-1,3-dimethyluracil，接著將此反應應用在6-cyanouridine 上，可以得到6-(tetrazol-5-yl)uridine 的產物。最後我們將六位腈基化合物與 hydroxylamine 反應形成 oxime，接著與苯環對位 (para) 具不同官能基的苯醯氯進行合環反應，可得到合環成為6-(5-phenyl-1,2,4-oxadiazol-3-yl)uridine 的衍生物。
這些六位具有取代基 uridine 衍生物，有潛力成為 ODCase 的抑制劑，未來將會進一步進行生物活性評估。

The focus of this thesis is the synthesis of derivatives for 6-aminouridine and 6-(1,2,4-oxadiazol-3-yl)uridine as a potential inhibitors for orotidine 5’-monophosphate decarboxylase (ODCase).

The 6-Cyano-1,3-dimethyluracil was chosen as the reaction model to investigate the substitution reaction with alkylamines as underwent nucleophiles. Our studies have shown that 6-cyano-1,3-dimethyluracil substitution reaction only with primary amines with primary alkyl substitutes. Finally, the reaction was applied for the synthesis of several 6-alkylaminouridine derivatives.

Furthermore, 6-Cyano-1,3-dimethyluracil as the starting material underwent click reaction with sodium azide to give 6-(tetrazol-5-yl)-1,3-dimethyluracil. The reaction was applied to prepare 6-(tetrazol-5-yl)uridine form 6-cyanouridine. Finally, the 6-cyanouridine derivatives was added hydroxylamine to give the corresponding oxime, and it was processed the cyclization reaction with the para-substituted benzoyl chlorides gave a series of 6-(5-phenyl-1,2,4-oxadiazol-3-yl)uridine derivatives
.
These 6-subsituted-uridine analogs are potential inhibitors for ODCase. Biological evaluation of the synthesized compounds will be investigated in the future.

縮寫對照表
英文摘要
中文摘要
第一章 緒論
1-1. 介紹 Orotidine 5’-monophosphate decarboxylase 1
1-2. ODCase的抑制劑與設計 4
第二章 6-alkylaminouridine 衍生物的設計與合成
2-1. 簡介 9
2-2. 實驗設計與合成 15
2-3. 實驗結果與討論 16
2-3.1. 6-CN-1,3-DMU的製備與親核基試劑的反應 16
2-3.2. 羥基具保護的6-CN-U 的製備與親核基試劑的反應 24
2-4. 總結 38
第三章 設計與合成6-(1,2,4-oxadiazole-3-yl)uridine 的衍生物
3-1. 簡介 39
3-2. 實驗設計與合成 40
3-3. 實驗結果與討論 40
3-3.1. 合成6-(tetrazol-5-yl)uridine 40
3-3.2. 合成6-(1,2,4-oxadiazol-3-yl)uridine 的衍生物 45
3-4. 總結 52
第四章 結論 53
第五章 實驗部分
5-1. 一般實驗處理 55
5-2. 儀器設備 55
5-3. 實驗步驟 57
參考文獻 88
光譜資料
Chien Lab Compound Characterization Checklist

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