合成 Glycolipids 與 Trehalose 的類似物

Abstract

This thesis consists of two chapters. Chapter I describes a total synthesis of a glyceroglycolipid and its truncated analogs, which simulates the core structure of thermophilic bacteria Meiothermus taiwanensis ATCC BAA-400. In our approach, we employed DMF-modulating glycosylation via pre-activation to construct 1,2-cis -glycosidic bond. We also synthesized the -Glc(1→1)-glycerol structure with excellent selective via conditional optimized DMF modulating glycosylation. Low concentration -selective glycosylation (LCG) method was employed to construct 1,2-trans -glycosidic linkage therefore the C2 participating group installation was avoided. Such glycosidic bonds were constructed with high efficiency and satisfactory stereoselectivity. Both the sequential and one pot glycosylation have been performed. Further installation of lipid chain in the oligosaccharide fragment and its global deprotection were performed succesfully. As no ester protecting groups were used in the carbohydrate backbone, so additional protection-deprotection steps were eschewed. Chapter II concerns the development of a new synthetic methodology which focuses on 1,1'-glycosylation to synthesize stereochemically pure trehalose analogs by using picoloyl protecting groups. By this method naturally occurring trehalose glycoconjugates can be achieved in an acceptable yield. We have reported the first synthesis of the natural product 4-trehalosamine and a triacylated trehalose glycolipid from Mycobacterium marinum. Further, we extended our work to prepare the hexasaccharide unit, the core structure of Lipooligosaccharide-IV (LOS-IV) found in Mycobacterium marinum. Hexasaccharide glucoside is comprising of a xylose unit, a rhamnose unit, two glucose unit and a trehalose unit. They are attached with eath other by β-, α-, β-, β-glycosidic linkage respectively. This hexasaccharide core was prepared by [2+2+2] convergent glycosylation approach and an orthogonal glycosylation strategy have been employed. All the glycosidic linkages have been constructed to efficiently to get the desired hexasaccharide as the major product.

This thesis consists of two chapters. Chapter I describes a total synthesis of a glyceroglycolipid and its truncated analogs, which simulates the core structure of thermophilic bacteria Meiothermus taiwanensis ATCC BAA-400. In our approach, we employed DMF-modulating glycosylation via pre-activation to construct 1,2-cis -glycosidic bond. We also synthesized the -Glc(1→1)-glycerol structure with excellent selective via conditional optimized DMF modulating glycosylation. Low concentration -selective glycosylation (LCG) method was employed to construct 1,2-trans -glycosidic linkage therefore the C2 participating group installation was avoided. Such glycosidic bonds were constructed with high efficiency and satisfactory stereoselectivity. Both the sequential and one pot glycosylation have been performed. Further installation of lipid chain in the oligosaccharide fragment and its global deprotection were performed succesfully. As no ester protecting groups were used in the carbohydrate backbone, so additional protection-deprotection steps were eschewed. Chapter II concerns the development of a new synthetic methodology which focuses on 1,1'-glycosylation to synthesize stereochemically pure trehalose analogs by using picoloyl protecting groups. By this method naturally occurring trehalose glycoconjugates can be achieved in an acceptable yield. We have reported the first synthesis of the natural product 4-trehalosamine and a triacylated trehalose glycolipid from Mycobacterium marinum. Further, we extended our work to prepare the hexasaccharide unit, the core structure of Lipooligosaccharide-IV (LOS-IV) found in Mycobacterium marinum. Hexasaccharide glucoside is comprising of a xylose unit, a rhamnose unit, two glucose unit and a trehalose unit. They are attached with eath other by β-, α-, β-, β-glycosidic linkage respectively. This hexasaccharide core was prepared by [2+2+2] convergent glycosylation approach and an orthogonal glycosylation strategy have been employed. All the glycosidic linkages have been constructed to efficiently to get the desired hexasaccharide as the major product.