【摘要】：大多數(shù)天然產(chǎn)物具有手性。隨著對手性物質(zhì)研究的深入,越來越多的手性化合物在藥物、精細化學品以及材料等方面得到了廣泛的使用。手性化合物中的對映異構(gòu)體具有很多相近的理化性質(zhì),但是,不同手性的對映體在生命體內(nèi)的表現(xiàn)有很大的差別。因此,獲得對生命體有益作用的異構(gòu)體對人們來說變得尤其重要。獲得這些單一光學純異構(gòu)體的一般方法是手性拆分、手性試劑合成、不對稱催化和生物合成。本文將分為兩大部分,分別對手性化合物的高效液相色譜的手性拆分和新型手性配體的合成及其不對稱催化進行論述。第一部分:手性氨基酸酰胺衍生物的液相色譜分離。在眾多的手性分離方法中,高效液相色譜手性固定相法使用越來越普遍,手性化合物大多能通過這種手段進行拆分。手性氨基酸酰胺類衍生物是一種應用廣泛的手性藥物中間體,但是使用手性固定相對氨基酸酰胺衍生物進行拆分的報道還很少,所以對它進行拆分研究很有意義。首先,采用課題組以前報道合成方法對10種氨基酸酰胺衍生物進行合成,然后對這10種氨基酸酰胺衍生物通過高效液相色譜手性固定相法進行手性拆分研究。在正相色譜條件下,改變不同的色譜條件,選出最優(yōu)分離條件。其次,在優(yōu)化后的色譜條件下,根據(jù)不同條件下的參數(shù)進行比較分析,根據(jù)化合物結(jié)構(gòu)的差別解釋不同基團對分離效果的影響,對手性拆分機理進行簡要的闡述。第二部分:N-芳基亞磺酰胺-烯手性配體的不對稱催化。手性配體在不對稱催化研究中扮演著十分重要的角色。目前,使用比較普遍的是具有“優(yōu)勢結(jié)構(gòu)”的膦、亞砜以及亞磺酰胺類等手性配體。本次實驗通過合成結(jié)構(gòu)簡單的亞磺酰胺配體進行催化反應研究。首先,在以前實驗的基礎(chǔ)上合成了幾種手性亞磺酰胺-烯配體。這些手性配體用于銠催化的芳基硼酸對環(huán)狀α,β-不飽和酮的共軛加成反應。以環(huán)己烯酮和芳基硼酸作為底物分別對手性配體、堿和溶劑的種類進行條件優(yōu)化。其次,在最優(yōu)的實驗條件下,分別對α,β-不飽和酮、硝基苯乙烯、苯偶酰、三氟苯乙酮等與一系列的芳基硼酸化合物進行反應普適性的考察。結(jié)果發(fā)現(xiàn),硝基苯乙烯不參與反應,除了α,β-不飽和酮以外,其他幾種化合物雖有部分反應,但是均不能和一系列的芳基硼酸有比較好的反應效果。綜上所述,本論文主要研究了十種手性氨基酸酰胺的液相色譜拆分,考察了手性固定相、柱溫、流動相等各種因素對手性氨基酸酰胺的色譜拆分影響,從熱力學角度對手性氨基酸酰胺在手性固定相上的拆分機理進行探討。本論文還對手性N-芳基亞磺酰胺-烯的手性配體用于銠催化的不對稱加成反應進行研究。
[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 偽, 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 偽, 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 偽, 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.
【學位授予單位】：成都理工大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：O621.251

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