Synthesis Of Monosaccharide Derivatives And Their Applications In Asymmetric Catalysis And Ion Fluorescent Recognition

Carbohydrates are abundant chiral pure compounds that widely distributed in nature. Owing to the diversity and complexity of their structures, synthesizing, characterization and application of sugar-based compounds have long been huge challenge by organic chemists. In view of economy, the thesis mainly focus on these problems list above, building chiral center, designing and synthesizing novel monosaccharide-based chiral amino alcohols, isothiocyanates and thioureas with extensive applications from carbohydrates which are inexpensive and readily available. In view of the fact that current saccharides are unsatisfied with their applications in biochemistry, asymmetric synthesis and analysis fields, the thesis is mainly concerned with applications of novel carbohydrate-based amino alcohols in enantioselective addition of diethylzinc to aldehydes reaction and the asymmetric direct aldol reaction, the application of novel carbohydrate-based thiourea in ions fluorescence recognition. The paper includes the following four parts:1. Designing and synthesizing of novel monosaccharide derivatives:(a) Designing and synthesizing of novel monosaccharide-based chiral β-amino alcohol and 1,3-amino alcohol:Firstly, based on the fact that five-membered cyclic sulfate can easily be substituted by nitrogen nucleophiles, two novel kinds of β-amino alcohols with amino group at C-5 position derived from D-fructose are synthesized by 6 steps reactions with selective protection and deprotection reactions, cyclic sulfated reaction and azide substitution reaction. Seven kinds of β-amino alcohols are synthesized by modifying the amino groups of two kinds of amino alcohols at the same time. Secondly, two kinds of novel 1,3-amino alcohols derived from sucrose are synthesized based on the fact that p-toluenesulfate can easily be substituted by nucleophilic reagent. Fructose-based azido sugar with azido group at C-6 position is synthesized through a series of hydrolyzing, selectively protected hydroxyl, esterification and azido substitution reactions. Moreover, a novel sorbitol-based azido derivative is synthesized by oxidation-reduction reactions with inversed hydroxyl configuration in C-4 position of glycosyl moiety. Two kinds of the chiral 1,3 amino alcohols are synthesized followed by reduction reactions.In the meanwhile, four kinds of β-amino alcohols are synthesized by modifying the amino groups of two types of 1,3-amino alcohols. Carbohydrate-based amino alcohols synthesizing in this paper with functional groups of amino and hydroxyl group have potentially broad applications in asymmetric synthesis and biochemistry.(b) Designing and synthesizing of monosaccharide-based isothiocyanates and thioureas:The synthesis of the precursor compound isothiocyanate is studied firstly. CS2/DCC is introduced firstly for synthesizing two types of novel carbohydrate-based isothiocyanates from full-protected glucosamine and glucose-based amino alcohol, and the yield is up to 90%. Secondly,8 types of novel glucosamine-derived thioureas are synthesized under different conditions by the reactions between the former carbohydrate-based isothiocyanate and 8 kinds of primary amines, and the yield is up to 94%. At last, according to the former study for the synthesis of thiourea in this thesis, a novel carbohydrate-based thiourea fluorescent compound with carbohydrate and fluorescent group connected by thiourea group is efficiently synthesized by peracetylated glucose isothiocyanate and rhodamine hydrazide. The characteristics of thiourea and carbohydrate make the sugar-based thioureas synthesized in this paper have extensive utilizations in asymmetric synthesis, biological, analysis and other field.2. The structural identification of novel monosaccharide derivatives:The paper has synthesized a series of novel monosaccharide derived chiral amino alcohols and thiourea compounds, confirming the configuration of this compounds can provide experimental data and analysis method for the further study. This thesis selects some representative compounds to identify their structure by NMR and ESI-MS techniques. The structures of novel (3-amino alcohols derived from D-fructose is identified by one-dimensional NMR, ESI-MS and two-dimensional NMR techniques, the results show that the structures are consistent with the designing compounds. the structure of novel monosaccharide 1,3-amino alcohol is determined indirectly by analyzing of its structural characteristics and comparing the 1H NMR and the value of J3,4 of two precursor compounds (azido sugar), the results show that the configurations of hydroxy group at C-4 position of sorbitol-based 1,3-amino alcohol and fructose-based 1,3-amino alcohol are opposite. Determining the structure of peracetylated glucose rhodamine thiourea to represent the structural identification of novel glucose-based thioureas by comparing the 1H NMR of its precursor (sugar-based isothiocyanate) with the structural analysis, the structure is finally determined with 13C NMR and ESI-MS as assistant technology.3. The applications of novel carbohydrate-based amino alcohols in asymmetric catalysis:(a) Novel carbohydrate-based chiral amino alcohols applied in asymmetric addition of diethylzinc to aldehyde reactions:Asymmetric addition of diethylzinc to aldehyde reaction is investigated firstly with amino-substituted P-amino alcohols and 1,3-amino alcohols synthesized in this thesis as chiral ligands for the consideration of ligands structure influences. The reaction is studied by changing amino alcohol ligands and their amount, reaction temperature, reaction solvent, and the amount of the cocatalyst Ti(Oi-Pr)4. It turned out that:By optimizing the conditions and expanding the substrate, amino alcohol with morpholine as amino-substituted group as chiral ligand getting highest yield that up to 94%, and the ee values up to 71%. The results show that chiral amino alcohol ligands synthesized in this thesis can be applied for the synthesis of chiral secondary alcohol that hard to synthesize by chiral separation, the study provides important experimental basis for the applications of newly monosaccharide-based amino alcohols(b) Novel carbohydrate-based chiral amino alcohols applied in asymmetric direct aldol reactions:Four kinds of synthesized β-amino alcohols and 1,3-amino alcohols with free amino groups are employed to catalyze the asymmetric direct aldol reaction between 3-nitrobenzaldehyde and cyclohexanone. The reaction is optimized by changing the amino alcohol ligands and their amount, reaction temperature, reaction solvent, and the amount of the additions. It turned out that:By employing optimum conditions to different asymmetric aldol reactions of aldehydes and ketones, the results show that P-amino alcohol/p-nitrophenol co-catalyst system can improve the yield and enantioselectivity of reactions, the yield is up to 98%, ee values up to 87%. It is also found that β-amino alcohol can be recycled many times to catalyze the reaction. By studying the reaction mechanism, we have first proposed β-amino alcohol/ p-nitrophenol co-catalyst system for the selective asymmetric synthesis of chiral secondary alcohols by hydrogen-bond interaction mechanism. The results show that chiral amino alcohol ligands synthesized in this thesis can be applied for the synthesis of chiral secondary alcohols that exist in complex compounds. Studying the mechanism of amino alcohol/phenolic catalytic system provides a theoretical basis for further research development.4. Novel monosaccharide thiourea fluorescence probe applied in ion fluorescent recognition:In view of the fact that fluorescent probes have shortcomings with poor water solubility and cell permeability in existing technology, the paper is intend to use the synthesized sugar-based rhodamine thiourea for Hg2+ fluorescent recognition. The results reveal that the compound can be used for Hg2+ identification in water and cannot be interfered by most of the ions, the Hg2+ chemodosimeter has a 1:1 stoichiometry, the probe can be used for recognizing the minimum allowable of Hg2+ in water, and the probe has a good fluorescent image expressing in cells for Hg2+ detection. In addition, the thesis investigates the mechanism of the probe for the efficient recognizing of Hg2+in water by ESI-MS technology and cyclic voltammetry method which provide theoretical basis for the designing and synthesizing of such compounds, the results reveal that Hg2+ caused an irreversible reaction with fluorescence enhancement. The results may provide experimental and theoretical basis for further study of carbohydrate-based thiourea fluorescent compounds acting in biological field.