發(fā)布時(shí)間：2019-07-09 07:39

【摘要】：手性胺是手性碳與氮原子相連的一類非常有意義的化合物。它們是很多化合物的中間體,在醫(yī)藥、農(nóng)藥、食品等領(lǐng)域有著廣泛的應(yīng)用。因此,用不對(duì)稱合成法直接制備這類手性化合物十分重要。本文對(duì)手性胺的不對(duì)稱合成作了初步的探討,內(nèi)容主要分為兩章。第一章是概括近年來(lái)亞胺不對(duì)稱還原的研究進(jìn)展,主要是布朗斯特酸和路易斯堿兩類有機(jī)小分子催化劑催化的(酮)亞胺還原的研究概況。第二章是在課題組前人工作的基礎(chǔ)上,繼續(xù)探究軸手性雙咔啉氮氧化物對(duì)酮亞胺的不對(duì)稱還原活性。我們首先在C-3,C-3′位以酰胺的形式結(jié)合不同的手性氨基酸甲酯,發(fā)現(xiàn)除脯氨酸甲酯取代基酰胺外,其它酰胺均具有兩套~1H和~(13)C核磁譜數(shù)據(jù),這似乎是混合物譜圖。但是通過(guò)進(jìn)一步分析,證明其為單一的手性酰胺。在考察其對(duì)酮亞胺的催化效果后,發(fā)現(xiàn)脯氨酸甲酯取代基酰胺有67%ee。在此基礎(chǔ)上,將酰胺的氮進(jìn)一步氧化生成軸手性雙咔啉N,N′-雙氧型催化劑,并考察了其在酮亞胺的不對(duì)稱催化還原反應(yīng)中的對(duì)映選擇性。實(shí)驗(yàn)結(jié)果表明:該反應(yīng)能夠在溫和條件(0℃)下于16-24 h內(nèi)順利完成,并有可觀的產(chǎn)率(90%)。當(dāng)?shù)孜锞哂泄╇娮踊鶗r(shí),反應(yīng)的對(duì)映選擇性普遍較好(70%ee)。其中C-3和C-3′位具有苯丙氨酸甲酯取代基的雙咔啉N,N′-雙氧化物具有最佳的對(duì)映選擇性(80%)。綜上所述,本研究設(shè)計(jì)合成了結(jié)構(gòu)新穎、性能良好的軸手性雙咔啉類催化劑。不僅篩選出了最優(yōu)催化劑和催化條件,還對(duì)底物進(jìn)行了擴(kuò)展,在此基礎(chǔ)上對(duì)反應(yīng)機(jī)理進(jìn)行了初步探討和研究,這為催化劑的后續(xù)開(kāi)發(fā)和應(yīng)用提供了理論和實(shí)驗(yàn)基礎(chǔ)。
文內(nèi)圖片：
圖片說(shuō)明：典型手性胺藥物
[Abstract]:Chiral amines are a kind of very meaningful compounds which are linked by chiral carbon to nitrogen atoms. They are intermediates of many compounds, and have wide application in the fields of medicine, pesticide, food and the like. Therefore, it is important to prepare such chiral compounds directly by asymmetric synthesis. In this paper, the asymmetric synthesis of the chiral amine in this paper is mainly discussed, and the content is mainly divided into two chapters. The first chapter is an overview of the research on the asymmetric reduction of the imines in recent years, mainly the research on the reduction of the (ketone) imine catalyzed by the two kinds of organic small molecular catalysts of the Bronsted acid and the Lewis base. The second chapter, on the basis of the previous work of the research group, continues to explore the asymmetric reduction activity of the chiral dicyandiamide on the ketoimine. We first combined different chiral amino acid methyl esters in the form of C-3 and C-3, and found that the other alicyclic amines have two sets of ~ 1H and ~ (13) C nuclear magnetic spectrum data, which appears to be the spectrogram of the mixture. But by further analysis it is shown that it is a single chiral polar amine. After examining its catalytic effect on the ketoimine, it was found that the methyl ester of the proline methyl ester was 67% ee. On the basis of this, the N, N-, N-, and N-type catalysts for the further oxidation of the amine with nitrogen were carried out, and their enantioselectivity in the asymmetric catalytic reduction of the ketoimine was investigated. The experimental results show that the reaction can be successfully completed in the range of 16-24 h under mild conditions (0.degree. C.) and has a considerable yield (90%). When the substrate has an electron donor, the enantioselectivity of the reaction is generally good (70% ee). In which the C-3 and the C-3 have the optimum enantioselectivity (80%) of the dicyandiamide N, N--dioxides with the phenylalanine methyl ester substituent. To sum up, the present study has been designed and synthesized a new-structure, well-behaved, chiral, double-polar-type catalyst. Not only the optimal catalyst and the catalytic conditions are selected, but also the substrate is expanded, and the mechanism of the reaction is discussed and studied, which provides a theoretical and experimental basis for the subsequent development and application of the catalyst.
【學(xué)位授予單位】：河北大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：O621.251

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本文編號(hào)：2511981