Study On Synthesis N-Glycan Of The Bisecting Type And It's Application

Cancer is a class of diseases which endangers human life and quality of life. Until now, the mechanism of cancer has not been illuminated, nor has the ideal method and drug to cure cancer. It has been suggested that bisecting N-glycans depress the metastasis of cancer. Although this conclusion has not been clearly identified, it may become a valuable approach to depress cancer metastasis. The research on the bioinformation function of bisecting N-glycans on cancer metastasis will provide a new target for anti-cancer drug. This research accomplished the synthesis of complicated bisecting N-glycans and extended the application of the new method: 1. Finding a new highly convenient route of D-talose synthesis and its acetylation derivates by hydroxy epimerization; 2. Protecting 2,3-dihydroxyl groups ofβ-D-glucopyranoside regioselectively by applying the new 4,6-O-benzylidene- protected-1,2-orthoesters strategy.Study on Synthesis N-Glycans of the Bisecting Type1 Though design and synthesis of compound model M1, the connection sequence problem of three branch of bisecting N-glycans was solved by connecting the 1→3 branch first, then the 1→4 branch, and 1→6 branch finally. As a result, the first choke for the synthesis of bisecting N-glycans was solved.2. The fragment withβ-D-mannoside was synthesized by directβ-D-mannoside coupling method, oxidation/reduction method and SN2 inversion method in sequence. A new highly convenient route for the core trisaccharide of N-glycans construction was found by the SN2 inversion method. And it is the most convenient route which has been reported until now. The second choke point for the synthesis of bisected N-glycans was resolved.3. Three substituent fragments of bisecting N-glycans-Compound B, Compound C and Compound D were synthesized. Among them, Compound B and Compound D were synthesized for the first time.4. Though adopting the tactic of convergent block synthesis, this paper synthesized two bisecting N-glycans with 49 steps in total, 5.2% yield for 33 steps in filiform, and 48 steps in total, 6.5% yield for 32 steps in filiform.Synthesis of Talose and its Acetylation DerivatesA new route for the synthesis of talose and its acetylation derivates was found by 3 steps using galactose as starting material. And two acetylation derivates of talose could be used as starting chiral reagents for other compounds. Study on the Synthesis of 4,6-O-Benzylidene-protected-1,2-orthoesters and ItsApplication.1. Three types of 4,6-O-benzylidene-protected-thioglycoside were designed to react with methanol to give orthoesters. Then the orthoesters were hydrolyzed after the protecting group of OH-3 was converted to other protecting group. As a result, the glycosyl fragment with 2,3 hydroxyls protected by different groups was obtained. In this section, the choke point for regioselective protection of 2,3 hydroxyls of glucoside was resolved.2. We found the reaction requirement for the synthesis of 4,6-O-benzylidene -protected-1,2-orthoesters. Moreover, we discovered that chloromethyl-4,6-O- benzylidene-protected-1,2-orthoesters were more stable than other types. Though obtaining two types of monocrystal configuration for 4,6-O-benzylidene- protected-1,2-orthoesters and analyzing the conformation of the monocrystal using single crystal diffraction.