臺灣博碩士論文加值系統

為了得到具有強力的抗過敏、抗發炎和抗下痢活性的化合物，著者以2-benzyloxybenzaldehyde為先導化合物，著手進行一系列2-substituted benzyloxy benzoic acid及其衍生物之合成。2-substituted benzyloxy benzonitriles 17-25, 2-substituted benzyloxy 2-methylbenzenes 26-29, 2-substituted benzyloxy phenyl methanols 30-33, 2-substituted benzyloxy benzoates 34-41, 2-substituted benzyloxy benzamides 42-44和2-substituted benzylamino benzoates 45-55是由substituted benzyl chloride在無水碳酸鉀及無水碘化鉀催化下，分別和2-氰基酚，鄰甲酚，柳酸，水楊酸甲酯，水楊醯胺，鄰氨基苯甲酸乙酯及2-氨基-4, 5-二甲氧基苯甲酸甲酯進行benzylation而得，另外，2-substituted benzyloxy benzoic acids 56-64及2-substituted benzylamino benzoic acids 65-75則是應用氫氧化鈉與相關之化合物進一步進行水解反應而得。將所合成之標的化合物進行生物活性之評估，發現2-substituted benzyloxy benzoic acid及其相關化合物對於抗發炎、抗過敏較不具活性。然而，2-[(4-methoxybenzyl)oxy] benzoic acid (64)和2-[(4-chlorobenzyl)amino] benzoic acid (68)對抗下痢則具有顯著的活性表現，值得進一步探討。

In order to obtain novel compounds with potent anti-inflammatory, anti-allergic and anti-diarrhea activities, 2-benzyloxybenzaldehyde was used as the lead compound, and 2-substituted benzyloxy benzoic acid derivatives were synthesized.
2-substituted benzyloxy benzonitriles 17-25, 2-substituted benzyloxy 2-methylbenzenes 26-29, 2-substituted benzyloxy phenyl methanols 30-33, 2-substituted benzyloxy benzoates 34-41, 2-substituted benzyloxy benzamides 42-44 and 2-substituted benzylamino benzoates 45-55 were synthesized by the benzylation with potassium carbonate and potassium iodide through the substituted benzyl chloride react with 2-cyanophenol, o-cresol, saligenin, methyl salicylate, salicylamide, ethyl anthranilate and methyl 2-amino-4,5- dimethoxybenzoate respectively. Then, the related compounds were hydrolyzed by sodium hydroxide to give 2-substituted benzyloxy benzoic acids 56-64 and 2-substituted benzylamino benzoic acids 65-75.
After screening for their biological activities, most of them have no anti-inflammatory and anti-allergic activities. However, 2-[(4-methoxybenzyl) oxy] benzoic acid (64) and 2-[(4-chlorobenzyl) amino] benzoic acid (68) showed significant anti-diarrhea activities and worthy for further investigation.

第一章 緒論
第一節 細菌性下痢之病理………………………………………… 1
第二節 肥胖細胞與嗜中性白血球之生理功能…………… 4
第三節 小神經膠質細胞之生理功能……………………………… 6
第四節 巨噬細胞之生理功能…………………………………….. 7
第五節 研究動機與目的…………………………………………… 8
第二章 結果與討論
第一節 化學合成
壹、 2-Substituted benzyloxy benzonitriles 17-25之合成…….. 9
貳、 2-Substituted benzyloxy 2-methylbenzenes 26-29
2-Substituted benzyloxy phenyl methanols 30-33
2-Substituted benzyloxy benzoates 34-41
2-Substituted benzyloxy benzamides 42-44之合成……… 18
參、 2-Substituted benzylamino benzoates 45-55之合成……… 20
肆、 2-Substituted benzyloxy benzoic acids 56-64
2-substituted benzylamino benzoic acids 65-75之合成...… 21
第二節 藥理活性試驗結果
壹、 抑制LTB與GM1-receptor結合之活性…………………. 31
貳、 嗜中性白血球脫顆粒反應之抑制活性…………………... 41
參、 嗜中性白血球過氧化物形成之抑制活性………………... 46
肆、 肥胖細胞脫顆粒反應之抑制活性………………………... 52
伍、 一氧化氮蓄積之抑制活性………………………………... 57
陸、 TNF-α形成之抑制活性………………………………….. 60
第三章 結論……………………………………………………………... 62
第四章 實驗部分
第一節 試藥、溶媒與材料…………………………………………. 64
第二節 重要儀器……………………………………………………. 66
第三節 化學合成方法………………………………………………. 68
第四節 藥理試驗方法…………………………………………. 107
參考文獻……………………………………………………………… 112
圖譜…………………………………………………………………… 120

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