| Among sucrose derivatives,sucralose is one of the best high-intensity sweeteners with good properties,such as non-nutrition,good flavor,high temperature stability and safety.Among the reported methods for regioselective synthesis of Sucralose in industry,the sucrose alkyl 4,6-orthoacylates method and dibutyltin oxide method are most widely used.However,the specificity of these methods is not high enough resulting in a major product and some other byproducts.Meanwhile,conditions such as catalyst,solvent and temperature can greatly affect the kinds and yields of the products,and usually need to be optimized to achieve maximum regioselectivity.Establishing a fast and sensitive method to detect the products of the synthesis process qualitatively and quantitatively is especially important for the optimization of synthesis technologies and control of reaction.The existing analytical methods include thin chromatography,HPLC with UV or refractive index(RI)detector.These methods are not sensitive enough or time consuming.On the other hand little work has been done on the structure identification of the byproducts,which is important for the optimization of synthesis technologies.In this work,fast and sensitive analytical methods such as HPLC coupled with evaporative light scattering detection(ELSD)and HPLC-on-line hydrolysis-pulsed amperometric detection(PAD)were established to monitor the synthesis process.Many by-products have been isolated and their structures have been studied and elucidated based on 1H NMR,13C NMR,2D NMR and MS for the first time.Chapter one comprised a brief introduction of sucrochemistry and sucrose derivatives and a comprehensive review of the discovery and property of sucralose,synthesis methods and analytical methods used to monitor the synthesis process.The shortcoming of the existing analytical methods was pointed out.Finally the new analytical methods and the importance of structure identification of the byproducts for the optimization of synthesis technologies were also proposed.In chapter two,sucrose-6-acetate was synthesized using alkyl 4,6-orthoacylates method and dibutyltin oxide method.HPLC-ELSD methods were established to monitor every reaction step including cyclization,hydrolysis and migration of acetyl.The structures of the byproducts of the cyclization reaction were predicted with HPLC-MS analysis for the first time.In chapter three,the major product and by products in crude sucrose-6-acetate were separated completely for the first time.Then they were all isolated and purified with LC followed by semi-preparative HPLC,their chemical structures were identified by 1D,2D NMR and LC-MS as sucrose,2-O-acetyl sucrose,3-O-acetyl sucrose,6-O-acetyl sucrose,2,6-di-O-acetyl sucrose,4,6-di-O-acetyl sucrose,3,6-di-O-acetyl sucrose,1',6-di-O-acetyl sucrose and 6',6-di-O-acetyl sucrose.In chapter four,a simple and sensitive method was developed for analysis of sucrose and sucrose acetate regio-isomers in crude sucrose-6-acetate product by on-line hydrolysis-liquid chromatography-pulsed amperometric detection.Quantification of sucrose acetate regio-isomers was achieved by on-line alkaline hydrolysis of sucrose acetates to liberate sucrose,and then detected by PAD for indirect estimation of the sucrose acetates content.This method overcomes the difficulty in quantification of sucrose acetate regio-isomers in the absence of regio-isomer standards for calibration.In chapter five,the process of the selective chlorination have been studied i n detail.A HPLC-ELSD method was established to monitor chlorination reactio n and several by-products have been isolated and their structures have been ide ntified based on 1H NMR,13C NMR,2D NMR and MS for the first time.Th e structures of the by products such as 4,6'-dichloro-4,6'-diceoxygalactosucrose-6-acetate,1',6'-dichloro-1',6'-dideoxysucrose-6-acetate,1',4-dichloro-1',4-dideoxyga lactosurose-6,6'-diacetate,4,1',6'-trichloro-4,1',6'-trideoxysucrose-6-acetate,1',6,6'-trichloro-1',6,6'-trideoxysucrose-4-acetate,1',6,6'-trichloro-1',6,6'-trideoxysucrose-3-acetate,4,6,1',6'-tetrachloro-4,6,1',6'-tetradeoxygalactosucrose and so on were identified.In chapter six,quantification of related compounds in sucralose is often hampe red by the lack of commercially available standards.In this work,nine related compounds including 1'6,6'-trichloro-1',6,6'-trideoxysucrose,1',4-dichloro-1',4-di deoxygalactosurose,4,6'-dichloro-4,6'-diceoxygalactosucrose,1',6'-dichloro-1',6'-did eoxysucrose,3',6-anhydro-1',4-dichloro-1',4-dideoxygalactosucrose,1,6-dichloro-1,6-dideoxy-b-D-fructofuranose,4-chloro-4-deoxya-D-galactopyranose,4,1',6'-trichlor o-4,1',6'-trideoxysucrose,4,6,1,6'-tetrachloro-4,6,1',6'-tetradeoxygalactosucrose were purified(purity>97%)and identified by LC-MS and NMR,then a rapid and simple HPLC-ELSD method has been developed for the simultaneous det ermination of sucralose and related compounds... |
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