酶催化、光催化构建C-C键的绿色合成方法研究

发布时间：2018-05-26 16:24

本文选题：绿色化学 + 酶的多功能性　；参考：《西南大学》2017年硕士论文

【摘要】：酶是生命体中普遍存在且具有重要催化作用的物质,具有高效性、专一性。不仅如此,酶可被生物降解,环境友好,副产品少,低能量需求使其成为极具吸引力的绿色生物催化剂。近年来,科学家们陆续发现酶具有催化非天然反应或作用于非天然底物的能力,这种现象叫做酶的多功能性。已经有很多关于酶的催化多功能性的例子被报道,比如aldol反应,Michael加成反应,Mannich反应,多组分串联反应,马氏加成反应以及α-氨基氰酰胺的不对称合成反应等。酶的催化多功能性在拓宽了酶的应用范围的同时也为有机合成提供了一种绿色的生物催化方法。本论文发展了木瓜蛋白酶催化aldol反应合成三氟甲基叔醇衍生物、猪胰脂肪酶和灰色链霉菌蛋白酶催化Michael反应合成罗丹宁及3,3-二取代氧化吲哚衍生物的绿色合成方法。可见光是一种廉价易得、来源丰富、绿色、可再生的清洁能源,具有绿色环保、使用简便、应用潜力巨大、范围广泛等优势。目前光氧化还原催化已经被有效地用于驱动有机合成领域中的化学转化,构建其它方法难以制备的分子。叶绿素是地球上储量最丰富的天然可见光光催化剂,它是大多数绿色植物叶绿体中主要的可见光受体。光合作用是自然界中最著名的化学反应之一,植物利用太阳光作为其能量来源在叶绿素的作用下将CO2和H2O转化成糖类。作为一种丰富,绿色和环保的光敏剂,叶绿素很少应用于光催化氧化还原反应。本论文报道了叶绿素作为光催化剂在可见光照射条件下催化环化反应合成四氢喹啉类衍生物的绿色合成方法。有些化学反应在无催化剂的条件下也能够很好地进行,大大降低了生产成本,同时也减少了对环境的污染,符合绿色化学的要求,具有重要的理论研究和实际应用价值。本论文发展了无催化剂条件下进行的直接氨化反应实现碳-氮键构建的绿色合成方法。不对称aldol反应作为最常见的碳-碳键构建方法之一,可以合成手性β-羟基羰基化合物。本论文第二章研究了在有机溶剂中木瓜蛋白酶催化三氟甲基酮和脂肪酮之间的aldol反应合成三氟甲基叔醇衍生物。经反应条件优化和底物扩展,目标产物收率收率范围在42-99%之间,对映选择性最高可达30%。同时提出了可能的反应机理,并通过抑制、失活等对照实验验证。该方法拓宽了木瓜蛋白酶的应用范围,同时为制备三氟甲基叔醇衍生物提供了一种绿色的合成途径。Michael加成反应是有机合成中构建碳-碳键的重要反应之一,在药物分子的发现和复杂天然产物的全合成过程中都可以作为一种非常有用的手段。本论文第三章对酶催化的Michael反应进行了研究。我们首次发现猪胰脂肪酶催化α,β-不饱和酮和罗丹宁之间Michael加成反应的新催化多功能性。通过对溶剂、含水量、底物投料比、pH值、溶剂总体积、酶量和温度在内的反应条件的优化,以及对底物范围的扩展,我们获得了23个罗丹宁类衍生物,收率范围在50-98%之间,非对映选择性最高可达99:1,对映选择性最高可达66%。本论文第四章对酶催化的Michael反应进行了研究。我们首次发现灰色链霉菌蛋白酶可以催化3-甲基羟吲哚、罗丹宁和马来酰亚胺之间的的Michael反应。通过一系列条件优化后进行底物普适性研究,各种底物均能够顺利地参与到反应中,我们共得到了19个目标产物,收率范围在50-99%之间。酶催化作为一种绿色的生物催化方法,探究其催化多功能性拓宽了酶的应用范围,酶的这些新催化多功能性的发现具有重要的应用价值。在本论文第五章中,我们发展了一种从N,N-二甲基苯胺和马来酰亚胺出发合成四氢喹啉衍生物的简单、绿色和高效的合成方法。该方法利用可见光和空气中的氧气作为绿色的试剂,天然色素叶绿素作为绿色的光敏剂,以简单的反应过程通过sp3 C-H键官能化及直接环化,以得到在药物和药物化学中具有重要研究价值的四氢喹啉衍生物。该反应底物适用范围广泛,共合成26个四氢喹啉类衍生物,目标产物收率范围在61-98%之间,同时对反应机理进行了深入探讨。碳-氮键的构建在有机化学中非常重要,但是目前关于无催化剂条件下进行的偶氮二甲酸酯与N,N-二甲基苯胺之间C(sp3)-H键的直接氨化反应还没有相关报道。无催化剂催化有机反应更符合绿色化学的理念。具有绿色、经济、条件温和、易于处理等优势。本论文第六章我们研究的无催化剂条件下进行的氨化反应的底物原子利用率达到100%,也符合绿色化学的研究目标。含有不同官能团的偶氮二甲酸酯与N,N-二甲基苯胺都能很好地进行反应,氨化产物收率范围在58-99%之间。将无催化剂催化与该氨化反应有机地结合,更加体现出绿色化学的研究理念,具有广阔的研究空间。
[Abstract]:Enzyme is a ubiquitous and important catalytic substance in the life body, which has high efficiency and specificity. The enzyme can be biodegraded, environmentally friendly, less by-products, and low energy demand makes it a very attractive green biocatalyst. In recent years, scientists have discovered that enzymes have been catalyzing non natural reactions or acting on non natural reactions. The ability of non natural substrates, this phenomenon is called the versatile activity of enzymes. Many examples of the catalytic versatile activity of enzymes have been reported, such as aldol reaction, Michael addition reaction, Mannich reaction, multicomponent series reaction, martensitic addition reaction and asymmetric synthesis of alpha aminocyanamide. In this paper, papain catalyzed aldol reaction to synthesize three fluoromethyl TERT alcohol derivatives, porcine pancreatic lipase and grey Streptomyces protease catalyzed Michael reaction to synthesize rodenning and 3,3- two substituted indole derivatives in this paper. Green synthesis method. Visible light is a kind of cheap and easy to obtain, rich source, green, renewable clean energy. It has the advantages of green environmental protection, simple use, great potential application and wide range. At present, photooxidation reduction catalysis has been effectively used to drive chemical conversion in organic synthesis collar and construct other methods which are difficult to prepare. Chlorophyll is the most abundant natural visible light photocatalyst on the earth. It is the main visible light receptor in most chloroplasts of green plants. Photosynthesis is one of the most famous chemical reactions in nature. Plants use sunlight as their energy source to convert CO2 and H2O into sugars under the action of chlorophyll. Rich, green and environment-friendly photosensitizer, chlorophyll is rarely used for photocatalytic redox reaction. This paper reported that chlorophyll is a green synthesis method for synthesis of four hydrogen quinoline derivatives by catalytic cyclization under visible light irradiation. Some chemical reactions can also be carried out well without catalyst. It has greatly reduced the cost of production, and also reduced the pollution of the environment. It accords with the requirements of green chemistry. It has important theoretical research and practical application value. In this paper, a green synthesis method for the construction of carbon nitrogen bond under the condition of direct ammoniation without catalyst is developed. The asymmetric aldol reaction is the most common carbon carbon. One of the key construction methods, chiral beta hydroxyl carbonyl compounds can be synthesized. The second chapter of this paper has studied the synthesis of three fluoromethyl TERT alcohol derivatives by the aldol reaction between three fluoromethyl ketone and fatty ketone in organic solvents. The yield and yield range of target products is in the range of 42-99% by reaction conditions and substrate expansion. The maximum enantioselectivity can be up to 30%. at the same time, and the possible reaction mechanism is proposed, which is verified by control experiments such as inhibition and inactivation. This method broadens the application range of papain, and provides a green synthesis route for the preparation of three fluoromethyl alcohol derivatives,.Michael addition reaction is important for the construction of carbon carbon bonds in organic synthesis. One of the reactions can be used as a very useful means in the discovery of drug molecules and the synthesis of complex natural products. The third chapter of this paper has been studied by enzyme catalyzed Michael reaction. We first found the new catalytic multifunctional pig pancreas lipase catalyzing the Michael addition reaction between alpha, beta unsaturated ketone and Luo Dan Ning. By optimizing the solvent, water content, substrate feeding ratio, pH value, total volume of solvent, enzyme and temperature, and extending the range of substrate, we obtained 23 rodenning derivatives with the yield range of 50-98%, the highest non enantioselectivity up to 99:1, and the highest enantioselectivity up to the fourth chapter of the paper. The Michael reaction catalyzed by enzymes was studied. We first found that the Michael reaction between 3- methyl hydroxyindole and Luo Danning and maleimide can be catalyzed by Streptomyces gray. The substrate universality was studied after a series of conditions, and all kinds of substrates were able to participate in the reaction. We got 19 Target product, yield range between 50-99%. Enzyme catalysis is a green biocatalysis method, exploring its catalytic multifunction broadening the application range of enzymes. The discovery of these new catalytic properties of enzymes has important application value. In the fifth chapter of this paper, we developed a kind from N, N- two methylaniline and maloyl. A simple, green and efficient synthesis of four hydrogen quinoline derivatives. This method uses visible light and oxygen in the air as a green reagent. The natural pigment chlorophyll acts as a green photosensitizer, and through the simple reaction process, the SP3 C-H bond is functionalized and direct cyclization, in order to obtain in drug and drug chemistry. Four hydrogen quinoline derivatives, which are important research values, are widely used in the synthesis of 26 four hydrogen quinoline derivatives. The yield range of target products is between 61-98% and the reaction mechanism is discussed. The construction of carbon nitrogen bond is very important in organic chemistry, but at present, it is carried out under no catalyst conditions. The direct ammonification reaction between azo two formate and N, N- two methyl aniline between C (SP3) -H bonds has not been reported. The catalytic organic reaction without catalyst is more in line with the idea of green chemistry. It has the advantages of green, economic, mild condition and easy to treat. The sixth chapter of this paper is the bottom of the ammoniation reaction under the catalyst without the condition of our study The utilization ratio of the atom is up to 100%, which is also in line with the research goal of green chemistry. The azo two formate containing different functional groups can react well with N, N- two methyl aniline, and the yield range of ammoniated product is between 58-99%. There is a wide space for research.
【学位授予单位】：西南大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.3

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