1. 設計與合成D-胺基酸氧化酶抑制劑以治療精神分裂症 2.藉由五羰基鐵介導芳基碘的羰基化以及微波輔助來一鍋化合成苯並噁唑和喹唑啉酮

Abstract

本論文分為二個部分 第一部分為研發D-胺基酸氧化酶抑制劑 (D-amino oxidase inhibitor, DAOI)，研究發現精神分裂症之患者腦中有過多的D-胺基酸氧化酶 (D-amino oxidase, DAO) ，因此抑制腦中過多的D-胺基酸氧化酶被認為可以有效治療精神分裂症，而且發現RS-D7具有很好的DAO抑制活性，因此我們以RS-D7為目標化合物，設計與合成一系列RS-D7類似物，並送測生物活性，期望可以找到更具效果之化合物；同時為了改善RS-D7溶解度不佳的問題，在此我們也對其結構進行修改，合成其前體藥物 (prodrug)，以改善其缺點以治療精神分裂症。 第二部分為一鍋化合成喹唑啉酮、苯並咪唑化合物，並利用微波輔助以縮短反應時間，在此我們以不同取代基的芳基碘化物以及鄰氨基/巰基/羥基硝基苯或鄰硝基苯甲醯胺為起始物，利用鈀金屬進行催化，並以五羰基鐵（Fe(CO)5）作為固態一氧化碳之來源，最終合成一系列之喹唑啉酮、苯並咪唑化合物，提供一個快速合成小分子雜環化合物的方法。

The first part is design and synthesis D- amino acid oxidase inhibitors (D-amino oxidase inhibitor, DAOI), the study found that patients with schizophrenia have brain excessive D- amino acid oxidase (D-amino oxidase, DAO) , thus suppressing excessive brain D- amino acid oxidase can be considered effective in the treatment of schizophrenia, and we found RS-D7 has good DAO inhibitory activity, therefore we used RS-D7 as the target compound, design and synthesis a series of RS-D7 analog and sent to test the biological activity and hoping that we can get more effective compound. On the other hand, in order to improve the poor solubility problems of RS-D7 , in which we have to modify its structure to improve the drawback. The second part : synthesis of benzazoles and quinazolinones is discovered by using iron pentacarbonyl as a reducing agent and solid carbon monoxide source under microwave irradiation. The reaction of substituted aryl iodides with o-amino/mercapto/hydroxyl nitrobenzenes and o-nitrobenzamides successfully delivered a wide variety of benzazoles and quinazolinones, respectively. The successive reactions proceed via iron pentacarbonyl mediated reduction of nitro to amine, carbonylative coupling of amines with aryl iodides followed by an intramolecular ring closure reaction. The diverse substrate scope with good to excellent yield makes this as a highly attractive strategy for the synthesis of benzazoles and quinazolinones.