氨基酸酰胺色谱分离和亚磺酰胺不对称催化

发布时间：2018-12-14 13:49

【摘要】：大多数天然产物具有手性。随着对手性物质研究的深入,越来越多的手性化合物在药物、精细化学品以及材料等方面得到了广泛的使用。手性化合物中的对映异构体具有很多相近的理化性质,但是,不同手性的对映体在生命体内的表现有很大的差别。因此,获得对生命体有益作用的异构体对人们来说变得尤其重要。获得这些单一光学纯异构体的一般方法是手性拆分、手性试剂合成、不对称催化和生物合成。本文将分为两大部分,分别对手性化合物的高效液相色谱的手性拆分和新型手性配体的合成及其不对称催化进行论述。第一部分:手性氨基酸酰胺衍生物的液相色谱分离。在众多的手性分离方法中,高效液相色谱手性固定相法使用越来越普遍,手性化合物大多能通过这种手段进行拆分。手性氨基酸酰胺类衍生物是一种应用广泛的手性药物中间体,但是使用手性固定相对氨基酸酰胺衍生物进行拆分的报道还很少,所以对它进行拆分研究很有意义。首先,采用课题组以前报道合成方法对10种氨基酸酰胺衍生物进行合成,然后对这10种氨基酸酰胺衍生物通过高效液相色谱手性固定相法进行手性拆分研究。在正相色谱条件下,改变不同的色谱条件,选出最优分离条件。其次,在优化后的色谱条件下,根据不同条件下的参数进行比较分析,根据化合物结构的差别解释不同基团对分离效果的影响,对手性拆分机理进行简要的阐述。第二部分:N-芳基亚磺酰胺-烯手性配体的不对称催化。手性配体在不对称催化研究中扮演着十分重要的角色。目前,使用比较普遍的是具有“优势结构”的膦、亚砜以及亚磺酰胺类等手性配体。本次实验通过合成结构简单的亚磺酰胺配体进行催化反应研究。首先,在以前实验的基础上合成了几种手性亚磺酰胺-烯配体。这些手性配体用于铑催化的芳基硼酸对环状α,β-不饱和酮的共轭加成反应。以环己烯酮和芳基硼酸作为底物分别对手性配体、碱和溶剂的种类进行条件优化。其次,在最优的实验条件下,分别对α,β-不饱和酮、硝基苯乙烯、苯偶酰、三氟苯乙酮等与一系列的芳基硼酸化合物进行反应普适性的考察。结果发现,硝基苯乙烯不参与反应,除了α,β-不饱和酮以外,其他几种化合物虽有部分反应,但是均不能和一系列的芳基硼酸有比较好的反应效果。综上所述,本论文主要研究了十种手性氨基酸酰胺的液相色谱拆分,考察了手性固定相、柱温、流动相等各种因素对手性氨基酸酰胺的色谱拆分影响,从热力学角度对手性氨基酸酰胺在手性固定相上的拆分机理进行探讨。本论文还对手性N-芳基亚磺酰胺-烯的手性配体用于铑催化的不对称加成反应进行研究。
[Abstract]:Most natural products are chiral. With the development of chiral substances, more and more chiral compounds have been widely used in drugs, fine chemicals and materials. The enantiomers of chiral compounds have a lot of similar physicochemical properties, but the enantiomers of different chiral compounds have very different performances in vivo. Therefore, it is particularly important for people to obtain isomers that are beneficial to life. The general methods for obtaining these single optical pure isomers are chiral resolution, chiral reagent synthesis, asymmetric catalysis and biosynthesis. In this paper, the chiral resolution of chiral compounds and the synthesis and asymmetric catalysis of novel chiral ligands are discussed. Part I: separation of chiral amino acid amide derivatives by liquid chromatography. Among many chiral separation methods, high performance liquid chromatography (HPLC) chiral stationary phase method is becoming more and more popular, and most chiral compounds can be separated by this method. Chiral amino acid amides are widely used as chiral drug intermediates, but there are few reports on the use of chiral immobilized relative amino acid amide derivatives, so it is meaningful to study the resolution of chiral amino acid amides. Firstly, 10 kinds of amino acid amide derivatives were synthesized by the method previously reported by our research group, and then the chiral resolution of 10 amino acid amide derivatives was studied by high performance liquid chromatography (HPLC) chiral stationary phase method. The optimal separation conditions were obtained by changing different chromatographic conditions under normal phase chromatography. Secondly, under the optimized chromatographic conditions, according to the parameters under different conditions, the effects of different groups on the separation effect were explained according to the structure of compounds, and the mechanism of chiral resolution was briefly explained. Part two: asymmetric catalysis of N-aryl sulfonamide-enene chiral ligands. Chiral ligands play an important role in asymmetric catalysis. At present, chiral ligands such as phosphine, sulfoxide and sulfonamide with "dominant structure" are widely used. The catalytic reaction was studied by the synthesis of simple sulfonamide ligands. Firstly, several chiral sulfonamide-enene ligands were synthesized on the basis of previous experiments. These chiral ligands are used for rhodium catalyzed conjugate addition of aryl boric acid to cyclic 伪, 尾 -unsaturated ketones. The chiral ligands, alkaloids and solvents were optimized using cyclohexenone and aryl boric acid as substrates. Secondly, under the optimal experimental conditions, the reaction properties of 伪, 尾 -unsaturated ketones, nitrobenzene ethylene, benzoyl, trifluoroacetophenone and a series of aryl boric acid compounds were investigated respectively. The results showed that nitrophenylene did not participate in the reaction, except 伪, 尾 -unsaturated ketones, some of the other compounds could not react with a series of aryl boric acid. To sum up, the liquid chromatographic resolution of ten chiral amino acid amides was studied in this paper. The effects of chiral stationary phase, column temperature and flow rate on the resolution of chiral amino acid amide were investigated. The resolution mechanism of chiral amino acid amide on chiral stationary phase was studied from the viewpoint of thermodynamics. The chiral ligands of chiral N-aryl sulfonamide-ene were also studied for rhodium-catalyzed asymmetric addition reaction.
【学位授予单位】：成都理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.251

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