| Carbohydrate is an important component in organism.Many sugar compounds have very high biological activity.Azasugar is a very special kind of sugar,and it has biological activity.In this paper,we selected ?-Galactosylceramide and Sitagliptin as the research object,and carried out the chemical synthesis method and the exploration of the change of biological activity by introducing or replacing the sugars with azasugar in active compounds.Firstly,we reviewed the current research on the structure activity relationship of the ?-Galactosylceramide analogues and the design and activity of Sitagliptin analogues.Secondly,in order to synthesis ?-Galactosylceramide analogues containing azasugar,we selected galactolactam and ?-1-vinyl-aza-galactose as azasugar donor to carry out a study on the construction of O-linked glycosidic bond and C-linked glycosidic bond based on cross-olefin metathesis(CM)reaction,but none of them have been obtained.We found that the O-linked glycosidic bond was very lability,while the CM reaction was ineffective to connect the donor and the acceptor.Thirdly,based on the concept of drug hybrid design,a class of Sitagliptin analogues containing azasugar were designed by computer simulation as a dipeptidyl peptidase 4(DPP-4)inhibitor.A general method for high efficiency and rapid synthesis of such compounds was constructed.Then SLD-2 and SLD-3 were synthesized and found that they can effectively inhibit DPP-4 in vitro bioassay(IC50 value: 0.97 ?M and 1.28 ?M,respectively)In this paper,the study of the application of azasugar to active compounds and the exploration of the method for the glycosidation of azasugar were explored.The research on the activity of azasugar-containing compounds has also achieved certain results?These work have reference significance for future related research.which is of significance for future related research work. |
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