陳焜銘Kwunmin Chen詹士賢CHAN, Shih-Hsien2020-10-19不公開2020-10-192020http://etds.lib.ntnu.edu.tw/cgi-bin/gs32/gsweb.cgi?o=dstdcdr&s=id=%22G060742075S%22.&%22.id.&http://rportal.lib.ntnu.edu.tw:80/handle/20.500.12235/111170有機不對稱催化是有機化學發展很重要的一環,有機催化的反應溫和,操作簡單,危險性低,而且原子的經濟效益高、廢棄物少,符合綠色化學及永續經營的概念,是一個具發展潛力的領域。光學異構物有不同的生物活性,沙利竇邁事件,讓科學家正視光學異構物在醫藥化學的重要性,促使化學家發展合成單一光學異構物的研究。有機不對稱催化反應,即是透過催化的方式,建構掌性的環境,合成具高光學活性的掌性結構化合物。 有機不對稱催化約從2000年開始蓬勃發展,在眾多的催化模式中,主要又可分為胺催化、氫鍵催化、布忍斯特酸催化…...等等,而本篇論文則是透過布忍斯特酸的催化模式,合成異噁唑啶衍生物。異噁唑的氮氧雜原子五環結構,不論是在天然界或是在藥物的開發,是很常見的架構,因此合成異噁唑啶衍生物的方法開發,對於藥物開發有幫助。 延續先前實驗室利用異噁錯啶為起始物,透過掌性布忍斯特酸催化,產生掌性相對離子中間體,利用吲哚當親核劑,進行Friedel-Crafts加成反應的概念,本次論文則利用吡咯做為親核劑,透過掌性磷酸催化劑的活化,對起始物異噁錯啶進行加成,成功建立四級碳中心,成功合成異噁錯衍生物,有良好的產率以及鏡像選擇性,盼在未來對於藥物開發或天然物合成有所幫助。Organic asymmetric catalysis is a very important part of the development of organic chemistry. The reaction of organic catalysis is mild, simple to operate, low risk, and the economic benefits of atoms are high, and the waste is small. It is in line with the concept of green chemistry and sustainable management. The organocatalystic development is potential. Optical isomers are different biological activities. The Thalidomide incident brought scientists to face the importance of optical isomers in medicinal chemistry, prompting chemists to develop research on the synthesis of single optical isomers. Organic asymmetric catalytic reaction is to construct a chiral environment through catalysis to synthesize chiral structure compounds with high optical activity. Organic asymmetric catalysis has been vigorously developing since 2000. Among the many catalysis modes, it can be divided into amine catalysis, hydrogen bond catalysis, and intolerant acid catalysis... etc., and this thesis is through catalytic mode of Brønsted acid to synthesis of isoxazolidine derivatives. The five-ring structure of the nitrogen and oxygen heteroatoms of isoxazole is a very common structure, whether in nature or in drug development. Therefore, the development of methods for synthesizing isoxazolidine derivatives is helpful for drug development. Continuing the previous laboratory’s concept of using hydroxyl dhydroisoxazole as the starting material and catalyzed by phosphoric acid to produce chiral counterion pairs intermediates, using indole as a nucleophile to carry out the Friedel-Crafts reaction. In thesis thesis, pyrrole was used as a nucleophile, through the activation of chiral phosphoric acid catalyst, the starting material hydroxyl dhydroisoxazole was added, and the quaternary carbon center was successfully established. The yied and enantioselectivity are good, hoping to be helpful to drug development or natural product synthesis in the future.有機不對稱催化異噁唑啶掌性磷酸催化劑布忍斯特酸相對離子對Organic asymmetric catalysisisoxazolidinechiral phosphoric acid catalystBrønsted acidcounterion pair有機不對稱催化合成異噁唑啶之衍生物Enantioselective synthesis of the isoxazolidine derivatives