摘要
氨基酸酰胺色谱分离和亚磺酰胺不对称催化
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。校园性教
工程年终总结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。
关键词：高效液相色谱手性固定相法氨基酸酰胺不对称催化手性亚磺酰胺烯烃配体铑催化
Abstract手绘画
Study on chromatographic enantioparation of amino acid amides and asymmetric catalysis of sulfinamides
Abstract
Most natural products have chirality.With the development of the rearch on the chiral substances,more and more chiral compounds have been widely ud in medicine,fine chemicals and chiral materials.The enantiomers of chiral compounds have many similar physical and chemical properties.However,there are great differences in the performance for different isomers in vivo.There
fore,it is very important for people to obtain isomers which have a good effect on animal bodies. The usual methods for obtaining the single optical isomers are chiral resolution, chiral reagent transformations,asymmetric catalysis,and biosynthesis.
This paper is divided into two parts:chromatographic enantioperation of chiral amino acid amide derivatives by HPLC and synthesis of new chiral ligands and their application in asymmetric catalysis.
Part one:Chromatographic enantioperation of chiral amino acid amide derivatives.
Among the many methods of chiral paration,chiral stationary pha method has been ud more and more widely.Chiral amino acid amide derivatives as chiral drug intermediates are widely ud.Although there are some studies on chromatographic enantioparation of amino acid derivatives,study on chiral resolution of amino acid amide derivatives on chiral stationary phras was rarely reported,chiral amino acid amide as important medicine intermediate,so study on paration by high performance liquid chromatography is also important.
First of all,ten amino acid amide derivatives were synthesized according to our group reported synthetic methods.Then,chromatographic enantioparation of the ten amino acid amide derivatives 活海参
under various conditions was elvaluated in high performance liquid chromatography(HPLC),and thus the optimized chromatographiccondition was obtained.
Secondly,under the optimized condition,the different conditions of the parameters are analyzed and compared.According to the difference of the structure of the compound,the effect of different groups on the paration effect was explained.A chromatographic enantioparation mechanism is propod.
Part two:The asymmetric catalysis of N-aryl sulfinamide-olefin chiral ligands.
Chiral ligands play an important role in asymmetric catalysis.At prent,the chiral ligands such as phosphines,sulfoxides,and sulfinamides are commonly ud as the"preveleged structures".
First,veral chiral sulfinamide-olefin ligands were synthesized bad on the reported procedures.And then the chiral ligands were ud in rhodim-catalyzed the conjugate addition of arylboric acid to cyclicα,β-unsaturated ketones.The conditions for the ligands,bas and solvents were screened with cyclohexene and aryl boric acid as substrates.
Secondly,under the optimized experimental conditions,the reaction of cyclohexenone,nitrostyrene,benzil,trifluoroacetophenone and a ries of aryl boric acids were investigated.The results showed that nitrostyrene was not involved in the reaction.Benzil and trifluoroacetophenone reacted with aryl boric acids,but only low enantiolectivities were obtained.
In summary,this thesis mainly studies HPLC chromatographic resolution of ten kinds of chiral amino acid amides.The effect of various factors,such as chiral solid phras,column temperature,mobile pha on chromatographic paration of chiral amino acid amides are investigated.The chiral paration mechanism of chiral amino acid amides on chiral solid phas are explored from thermokinetic point.Chiral N-arylsulfinamide-olefin ligands ud in rhodium-catalyzed enantiolective addition reactions are also studied in this thesis.
Keywords:HPLC,Chiral stationary phas,Amino acid amides,Asymmetric catalysis,Chiral sulfinamide-olefin ligands,Rhodium catalysis
目录
目录
摘要.............................................................................................................................III 第一部分手性氨基酸酰胺化合物的液相色谱分离 (1)
第1章绪论 (1)
1.1手性分离的重要性及意义 (1)
1.2手性分离方法 (3)
1.2.1结晶分离法 (3)
1.2.2化学拆分法 (4)
1.2.3生物法 (4)
1.2.4色谱分离法 (4)
1.2.4.1气相色谱法 (5)
1.2.4.2超临界流体色谱法 (5)
管理类专业
1.2.4.3薄层色谱法 (6)
滕州马铃薯1.2.4.4毛细管电泳色谱法 (6)
1.2.4.5高效液相色谱法 (6)
就当养条狗1.3高效液相色谱手性固定相法 (7)
1.3.1冠醚类手性固定相 (7)
1.3.2Pirkle型手性固定相 (8)
1.3.3环糊精类手性固定相 (9)
1.3.4多糖类手性固定相 (9)
1.4高效液相色谱手性固定相法分离机理及色谱参数 (10)
1.4.1分离机理 (10)
1.4.2色谱参数 (11)
1.5选题依据 (12)
第2章实验部分 (14)
2.1实验仪器及药品 (14)
2.1.1实验仪器 (14)
2.1.2实验药品 (14)
2.2手性氨基酸酰胺类化合物的合成 (15)
2.3色谱条件的优化 (17)
第3章结果与讨论 (18)
3.1代表产物的氢谱分析 (18)
3.2手性柱对分离效果的影响 (19)
3.3柱温对分离效果的影响 (22)
3.4流动相中异丙醇浓度对分离的影响 (25)
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3.5机理浅析 (29)
第4章结论 (30)
第二部分手性N-芳基亚磺酰胺烯烃配体的合成及不对称催化研究 (31)
第1章研究背景 (31)
1.1手性配体不对称催化的意义及反应 (31)
1.2手性配体及其研究进展 (32)
