Development And Application Of Novel Glycosylation Strategies Based On Interrupted Pummerer Reaction

Glycosides and their conjugates play extremely important roles in many physiological and pathogenic processes. Among them, more than 500 compounds have been developed as drugs to treat various deseases such as diabetes, virus infections, bacterial infections and cancer. However, owing to their structure complexities, with several chiral centers and many polar groups such as OH and NH2, it is extremely challenge to obtain enough highly pure glycosides and their conjugates from natural sources. As a consequence, the limited sample sources set a bottleneck to their structural and functional studies. Thus, development of new chemical approachs for the synthesis of glycosides is very important to the discovery of carbohydrate chemistry, glycobiology and carbohydrate-based drugs.This thesis demonstrated a development of new glycosylation method which is based on novel glycosyl donors with 2-(2-propylthiol)benzyl (PTB) and 2-(2-propylsulfinyl)benzyl (PSB) leaving groups. Initially, the latent O-glycosides,2-(2-propylthiol)benzyl (PTB) glycosides, were converted into the corresponding active glycosyl donors, 2-(2-propylsulfinyl)benzyl (PSB) glycosides, by a simple and efficient oxidation. Then, treatment of the active glycosyl donor and various acceptors with triflic anhydride provided the desired glycosides in good to excellent yields via an Interrupted Pummerer reaction mode. The efficient conversion between PTB and PSB functional groups achieved the effective transformation of latent glycosyl donors to active ones, providing the foundation for their application in latent-active glycosylation strategy. The glycosyl donor showed many advantages such as good stability and high reactivity. Moreover, the leaving group could be recycled (PSB-OH) and regenerated as the precursor (PTB-OH). With this newly developed method, a natural hepatoprotective glycoside-Leonoside F has been efficiently synthesized in a convergent [3+1] manner. The present total synthesis has led to the structural revision of this phenylethanoid glycoside. This study provided a new way towards oligosaccharide synthesis and laid the basis for further study on glycobiology and carbohydrate-based drugs.