高效液相色谱及联用技术分离分析蔗糖衍生物及结构表征
发布时间：2018-03-20 12:46
本文选题：蔗糖衍生物 切入点：三氯蔗糖 出处：《浙江大学》2017年博士论文 论文类型：学位论文
【摘要】：蔗糖衍生物三氯蔗糖是目前世界上性能最为优良的甜味剂之一。它具有非营养、稳定、高甜度、高安全性和风味好等诸多优点。工业上应用最为广泛的两种三氯蔗糖合成方法为原乙酸三甲酯法和有机锡法,然而这些方法的选择性都不够高,反应过程中有较多副产物生成。反应条件如催化剂,溶剂和温度对反应产物的种类和收率都有很大影响。因此通常需要对反应条件进行优化以便获得最高选择性。建立快速灵敏的定性定量分析方法监测每步反应对工艺优化和反应过程控制非常重要。目前已报导的分析方法主要有薄层色谱,液相色谱分离紫外或示差检测。这些方法繁琐费时或灵敏度低。另一方面对三氯蔗糖合成过程中副产物的分析鲜有文献报导。反应中相关杂质的结构确定对反应过程控制和合成工艺优化非常重要。本论文基于以上考虑,建立了快速灵敏的高效液相色谱-蒸发光散射检测(HPLC-ELSD)方法,高效液相色谱分离-在线水解-脉冲积分安培电化学检测系统,结合HPLC-MS和核磁共振等分析方法对每步反应的主产物和相关杂质进行了较为系统的定性定量研究。第一章介绍了蔗糖化学和蔗糖衍生物并综述了蔗糖衍生物三氯蔗糖的发现、结构特点、合成方法及合成过程中的分析方法。指出了目前分析方法的不足之处,提出了 HPLC-ELSD等分析方法的可行性和反应副产物的结构确定对合成工艺优化的重要性。第二章建立了HPLC-ELSD方法分析原酸酯法合成蔗糖-6-酯的环化,水解和酰基迁移各步反应,首次对环化过程中的主要产物和相关杂质进行了系统分离并经HPLC-MS分析初步推测各副产物的结构。第三章详细研究了蔗糖-6-乙酯反应液,首次对蔗糖-6-乙酯粗品中主产物和副产物进行了完全分离,并利用制备和半制备色谱对蔗糖-6-乙酯反应液中的主产物和相关单酯异构体,双酯异构体,蔗糖原料等杂质进行了分离纯化和结构研究。利用HPLC-MS和NMR确定它们的具体结构为:蔗糖、蔗糖-2-乙酯、蔗糖-3-乙酯、蔗糖-6-乙酯、2,6-蔗糖-二乙酯、4,6-蔗糖-二乙酯、3,6-蔗糖-二乙酯、1',6-蔗糖-二乙酯和6',6-蔗糖-二乙酯。第四章建立高效液相色谱分离-在线水解-脉冲积分安培电化学检测系统。将蔗糖酯通过在线水解转化成蔗糖,脉冲积分安培电化学检测,以蔗糖为标样,间接测定蔗糖-6-乙酯反应液中的蔗糖-6-酯和相关单酯异构体,双酯异构体等杂质含量,实现了蔗糖酯的无标样定量。解决了蔗糖酯因无商品化标样和蔗糖酯标样制备困难而难以准确定量的问题。第五章详细研究了选择性氯化的反应过程,建立了 HPLC-ELSD方法对蔗糖-6-乙酯氯化反应液中的主产物和相关杂质进行了分离;利用制备和半制备色谱对氯化反应中主要副产物进行了分离纯化并利用HPLC-MS和NMR确定它们的具体结构。最终确定了4,6'-二氯蔗糖-6-乙酯、1',6'-二氯蔗糖-6乙酯、4,1'-二氯蔗糖-6,6'-二乙酯、4,1' 6‘-三氯-4,1',6'-三脱氧蔗糖-6-乙酯、1',6',6-三氯蔗糖-4-乙酯、为1',6',6-三氯蔗糖-3-乙酯、4,6,1' 6‘-四氯-4,6,1',6'-四脱氧半乳蔗糖等主要副产物的具体结构。第六章通过柱色谱和半制备色谱分离纯化,经HPLC-MS,核磁共振分析确定结构,制备了三氯蔗糖中1',6,6'三氯-1'，6,6'-三脱氧蔗糖、1',4-二氯-1',4-二脱氧半乳蔗糖、4,6'-二氯-4,6' 二脱氧半乳蔗糖、1',6'-二氯-1',6'二脱氧蔗糖、3',6'-糖肝-1',4-二氯-1',4一脱氧半乳蔗糖、1,6-二氯-1,6-二脱氧-D-果糖、4-氯-4-脱氧-D-半乳糖,4,1',6'-三氯-4,1',6'-三脱氧蔗糖和4,6,1',6'-四氯-4,6,1',6'-四脱氧半乳蔗糖等相关杂质的标样。首次建立了 HPLC-ELSD法同时测定三氯蔗糖产品中三氯蔗糖和相关杂质含量。
[Abstract]:Three sucrose derivatives sucralose is currently the world's most excellent performance. It is one of the sweeteners non nutrition, stable, high sweetness, the advantages of high safety and good flavor. The industrial application of the two three sucralose synthesis method is widely trimethylorthoacetate method and organic tin method. However, these methods are not high selectivity, more by-products in the reaction process. The reaction conditions such as catalyst, solvent and temperature have great influence on the yield of species and reaction products. So usually the reaction conditions were optimized to obtain the highest selectivity. Establishment of qualitative and quantitative rapid and sensitive analytical method for the monitoring of each reaction is very important the reaction process optimization and process control. The current analytical methods have been reported mainly in TLC, UV separation or differential detection in liquid chromatography. These methods are tedious and time-consuming or low sensitivity There is little literature analysis reports. On the other hand, the synthesis process of sucralose three by-products in structure related impurities in the reaction. It is important to confirm the reaction process control and optimization of synthesis process. Based on the above consideration, a rapid and sensitive high performance liquid chromatography - evaporative light scattering detection (HPLC-ELSD) method, high performance liquid chromatographic separation - on-line hydrolysis and pulsed integrated amperometric electrochemical detection system, combined with HPLC-MS and 1H NMR analysis method of main products of each reaction and related impurities were qualitatively and quantitatively studied. The first chapter introduces the chemical and sucrose sucrose derivatives was reviewed in three sucrose sucrose derivatives, structural characteristics, analysis methods of synthesis and process. Analysis pointed out that the current deficiencies, put forward the feasibility and the reaction by-product HPLC-ELSD analysis method The structure of the importance of the synthesis optimization. In the second chapter, the HPLC-ELSD method is established for analysing cyclic orthoester synthesis of sucrose ester -6-, hydrolysis and acyl transfer reaction in each step, for the first time on the main product of cyclization process and related impurities were isolated and analyzed by HPLC-MS speculated that the structure of each side product. The third chapter studies the reaction of sucrose -6- acetate solution, for the first time on the main products and by-products of crude -6- acetate were sucrose completely separated, and the preparation and semi preparative chromatography on the main product of sucrose -6- ester in the reaction mixture and single ester isomers, double ester isomers, sugar and other raw materials the impurity was isolated and purified from the study of the structure. They determine the structure for the use of HPLC-MS and NMR: sucrose, sucrose ester -2-, sucrose -3- acetate, sucrose -6- acetate, ethyl - two 2,6- sucrose, two 4,6- sucrose - ethyl ester, sucrose 3,6- Two - 1'6- -, ethyl acetate and two 6' sucrose, two 6- sucrose acetate. The fourth chapter is to establish a high performance liquid chromatographic separation - on-line hydrolysis and pulsed integrated amperometric electrochemical detection system. Through on-line hydrolysis of sucrose ester into sucrose, integrated pulsed amperometric detection, using sucrose as the standard sample, the indirect determination of sucrose -6- -6- ethyl ester of sucrose in the reaction mixture and single ester isomers, double ester isomers and other impurities, standardless quantitative sucrose esters to achieve. To solve the sucrose ester because there is no commercial standard sample and standard sample preparation of sucrose ester difficult to accurately quantitative questions. The fifth chapter studies the reaction process of selective chlorination, HPLC-ELSD method was established for separation of main product of sucrose -6- ethyl chloride in the reaction solution and related impurities; preparation and semi preparative chromatography on the main by-product of chlorination was purified by using H PLC-MS鍜孨MR纭畾瀹冧滑鐨勫叿浣撶粨鏋，
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