Lewis Acid-activated Glycosylation Using O-acetaminoxy Glycosides As Glycosyl Donors

Carbohydrates play an important role in many biological and pathological processes in organisms.In-depth understanding of carbohydrate involvement will help in the research on glycobiology and carbohydrate drugs.These endogenous compounds are often present in low concentrations and micro-heterogeneous forms,making them extremely difficult to isolate and characterize.A large number of highly pure and well-defined oligosaccharides and glycoconjugates are generally prepared by chemical synthesis.The main focus in the chemical synthesis of carbohydrates is the construction of glycosidic bonds in glycosylation reactions.Therefore,the research on glycosylation is important for the development of the entire glycoscience.In recent years,the technology of microwave irradiation has been reported to increase the yield,shorten reaction time,change the regioselectivity and stereoselectivity of the reaction,and gradually become an increasingly popular method for chemists to quickly optimize reaction conditions and explore new reactions.In this thesis,we have developed a new glycosylation method,which is based on novel glycosyl donors with acetaminoxy leaving groups.This method can be applied to the rapid and efficient construction of O-glycosidic bond.Firstly,we selected the optimal reaction conditions:4.0 equiv.Cu?OTf?₂ as the activator,reacting at room temperature for 5 hours.Because of high equivalents of the activator and the long reaction time,we again optimized the reaction conditions with the microwave-assisted technology.Finally,we determined the optimal reaction conditions:1.5 equiv.SnCl₄ as the activator,reacting at 40 ^oC for 30 minutes or 2.0 equiv.Cu?OTf?₂ as the activator,reacting at 80^oC for 1 hour.This method has good substrate suitability and compatibility of protecting groups,which is suitable for various glycosyl donors such as galactose,glucose,rhamnose,mannose and ribose;and low-reactive,acid-sensitive receptors,and could generally achieve good to higher yields.Mechanism studies indicated that the byproduct from leaving group could precipitate from the solution in the form of a complex and is a traceless leaving group.This strategy is suitable for large-scale preparation of carbohydrate compounds.