本文選題：蔗糖衍生物　切入點(diǎn)：三氯蔗糖　出處：《浙江大學(xué)》2017年博士論文　論文類型：學(xué)位論文

【摘要】：蔗糖衍生物三氯蔗糖是目前世界上性能最為優(yōu)良的甜味劑之一。它具有非營(yíng)養(yǎng)、穩(wěn)定、高甜度、高安全性和風(fēng)味好等諸多優(yōu)點(diǎn)。工業(yè)上應(yīng)用最為廣泛的兩種三氯蔗糖合成方法為原乙酸三甲酯法和有機(jī)錫法,然而這些方法的選擇性都不夠高,反應(yīng)過程中有較多副產(chǎn)物生成。反應(yīng)條件如催化劑,溶劑和溫度對(duì)反應(yīng)產(chǎn)物的種類和收率都有很大影響。因此通常需要對(duì)反應(yīng)條件進(jìn)行優(yōu)化以便獲得最高選擇性。建立快速靈敏的定性定量分析方法監(jiān)測(cè)每步反應(yīng)對(duì)工藝優(yōu)化和反應(yīng)過程控制非常重要。目前已報(bào)導(dǎo)的分析方法主要有薄層色譜,液相色譜分離紫外或示差檢測(cè)。這些方法繁瑣費(fèi)時(shí)或靈敏度低。另一方面對(duì)三氯蔗糖合成過程中副產(chǎn)物的分析鮮有文獻(xiàn)報(bào)導(dǎo)。反應(yīng)中相關(guān)雜質(zhì)的結(jié)構(gòu)確定對(duì)反應(yīng)過程控制和合成工藝優(yōu)化非常重要。本論文基于以上考慮,建立了快速靈敏的高效液相色譜-蒸發(fā)光散射檢測(cè)(HPLC-ELSD)方法,高效液相色譜分離-在線水解-脈沖積分安培電化學(xué)檢測(cè)系統(tǒng),結(jié)合HPLC-MS和核磁共振等分析方法對(duì)每步反應(yīng)的主產(chǎn)物和相關(guān)雜質(zhì)進(jìn)行了較為系統(tǒng)的定性定量研究。第一章介紹了蔗糖化學(xué)和蔗糖衍生物并綜述了蔗糖衍生物三氯蔗糖的發(fā)現(xiàn)、結(jié)構(gòu)特點(diǎn)、合成方法及合成過程中的分析方法。指出了目前分析方法的不足之處,提出了 HPLC-ELSD等分析方法的可行性和反應(yīng)副產(chǎn)物的結(jié)構(gòu)確定對(duì)合成工藝優(yōu)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-酯的環(huán)化,水解和酰基遷移各步反應(yīng),首次對(duì)環(huán)化過程中的主要產(chǎn)物和相關(guān)雜質(zhì)進(jìn)行了系統(tǒng)分離并經(jīng)HPLC-MS分析初步推測(cè)各副產(chǎn)物的結(jié)構(gòu)。第三章詳細(xì)研究了蔗糖-6-乙酯反應(yīng)液,首次對(duì)蔗糖-6-乙酯粗品中主產(chǎn)物和副產(chǎn)物進(jìn)行了完全分離,并利用制備和半制備色譜對(duì)蔗糖-6-乙酯反應(yīng)液中的主產(chǎn)物和相關(guān)單酯異構(gòu)體,雙酯異構(gòu)體,蔗糖原料等雜質(zhì)進(jìn)行了分離純化和結(jié)構(gòu)研究。利用HPLC-MS和NMR確定它們的具體結(jié)構(gòu)為: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譜分離-在線水解-脈沖積分安培電化學(xué)檢測(cè)系統(tǒng)。將蔗糖酯通過在線水解轉(zhuǎn)化成蔗糖,脈沖積分安培電化學(xué)檢測(cè),以蔗糖為標(biāo)樣,間接測(cè)定蔗糖-6-乙酯反應(yīng)液中的蔗糖-6-酯和相關(guān)單酯異構(gòu)體,雙酯異構(gòu)體等雜質(zhì)含量,實(shí)現(xiàn)了蔗糖酯的無標(biāo)樣定量。解決了蔗糖酯因無商品化標(biāo)樣和蔗糖酯標(biāo)樣制備困難而難以準(zhǔn)確定量的問題。第五章詳細(xì)研究了選擇性氯化的反應(yīng)過程,建立了 HPLC-ELSD方法對(duì)蔗糖-6-乙酯氯化反應(yīng)液中的主產(chǎn)物和相關(guān)雜質(zhì)進(jìn)行了分離;利用制備和半制備色譜對(duì)氯化反應(yīng)中主要副產(chǎn)物進(jìn)行了分離純化并利用HPLC-MS和NMR確定它們的具體結(jié)構(gòu)。最終確定了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'-三脫氧蔗糖-6-乙酯、1',6',6-三氯蔗糖-4-乙酯、為1',6',6-三氯蔗糖-3-乙酯、4,6,1' 6‘-四氯-4,6,1',6'-四脫氧半乳蔗糖等主要副產(chǎn)物的具體結(jié)構(gòu)。第六章通過柱色譜和半制備色譜分離純化,經(jīng)HPLC-MS,核磁共振分析確定結(jié)構(gòu),制備了三氯蔗糖中1',6,6'三氯-1'，6,6'-三脫氧蔗糖、1',4-二氯-1',4-二脫氧半乳蔗糖、4,6'-二氯-4,6' 二脫氧半乳蔗糖、1',6'-二氯-1',6'二脫氧蔗糖、3',6'-糖肝-1',4-二氯-1',4一脫氧半乳蔗糖、1,6-二氯-1,6-二脫氧-D-果糖、4-氯-4-脫氧-D-半乳糖,4,1',6'-三氯-4,1',6'-三脫氧蔗糖和4,6,1',6'-四氯-4,6,1',6'-四脫氧半乳蔗糖等相關(guān)雜質(zhì)的標(biāo)樣。首次建立了 HPLC-ELSD法同時(shí)測(cè)定三氯蔗糖產(chǎn)品中三氯蔗糖和相關(guān)雜質(zhì)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紜畾瀹冧滑鐨勫叿浣撶粨鏋，

本文編號(hào)：1639157