Synthesis Of 1-deoxynojirimycin And Miglitol

Recent years, with the improvement of people's living standard, diabetes has become the third-largest non-communicable disease after cancer and angiocardiopathy in the world which threats human health seriously. Relative to the diabetes itself, the diabetes complications such as blindness or renal failure are usually terrible harmful to human bodies. More seriously, about 50% of diabetics die from heart disease or stroke caused by diabetes complications. Controlling diabetes is urgently needed. Among a lot of antidiabetic agents, a-glycosidase inhibitor drugs dominate the market with its significant effect and less side effect. They control blood sugar by inhibiting activity of the a-glycosidase enzymes, blocking the hydrolysis of polysaccharides from the source. 1-deoxynojirimycin, miglitol and its analogous compounds are all effective a-glucosidase inhibitors, and miglitol has becomed the first choice drug of antidiabetic agents. Due to many disadvantages of existing a-glucosidase inhibitors, such as less species, high production costs and expensive price, it is of great medical and economic significance to develop new synthetic route of 1-deoxynojirimycin and miglitol with improving the quality of drugs and reducing the production cost.The synthetic route of 1-deoxynojirimycin and miglitol had been optimized based on the traditional synthesis process. This route presents a new method to prepare azasugar by hydrolysis, oxidation and reductive amination reaction using 1,2:5,6-di-O-isopropylidene-D-glucofuranose as substrate. Meanwhile, we explore the selectively hydrolysis of di-/tri-O-isopropylidene derivatives of sugars and polyhydroxy alcohols, using S-CKT ?sulfonatcd carbon nanomaterials? as catalysts with good performance. The main work and conclusions of this thesis are summarized as follows:1. Selective hydrolysis of 1,2:5,6--Oisopropylidene-D-glucofuranose to 1,2-O-isopropylidene-a-D-glucofuranose with a high yield using S-CKT as catalyst, and the recoverability of S-CKT was investigated. This catalytic system has been successfully applied in the selective hydrolysis of other di-/tri-O-isopropylidene derivatives of sugars and polyhydroxy alcohols. The experimental results showed that the reaction system catalyzed by S-CKT could selective hydrolysis of isopropylidene derivatives of various polyols in relatively mild conditions with high yields. This system has wide substrate scope, simple reaction post-processing operation, easy product separation and good recoverability of catalyst, and has a good application prospect in the production of many mono/di-O-isopropylidene derivatives.2. The complex [?neocuproine?Pd-?OAc?]₂?OTf?₂ synthesized from neocuproine ?2,9-dimethyl-1,10-phenanthroline?, HOTf and Pd?OAc?₂, was used as a catalyst to the selective oxidation of several vicinal polyols with p-benzoquinone or O₂ as oxidant in the mixture of acetonitrile and water ?9:1, V:V?. This catalytic system was applied to the oxidation of several vicinal polyols including 1,2-O-isopropylidene-a-D-glucofuranose, 1-phenylethane-1,2-diol and 1,2-decanediol to afford corresponding a-hydroxy ketones in good yields. Especially for the selective oxidation of 1-phenylethane-1,2-diol, the chemical yield was up to 93%.3. A new synthesis route for 1-deoxynojirimycin and migltol had been developed. In this route,1-deoxynojirimycin and migltol were prepared through reductive animation of 5-amino-D-glucose respectively. Although the total yield was a little low than traditional methods, this new synthesis route significantly shortened to prepare the corresponding target product.