Pre-activation based glycosylation is a powerful method for synthesizing bioloigically important oligosaccharides. Chapter 1 summarized the progress in this area in recent years. This approach has unique characteristics compared to traditional oligosaccharide synthetic methods. This chapter discussed its chemoselectivity and stereoselectivity in details. Pre-activation based iterative one-pot synthesis greatly accelerated the oligosaccharide assembly process. To further improve the overall synthetic efficiency, we developed a new method which was described in Chapter 2. This new method combines one-pot synthesis and fluorous separation. After one-pot glycosylation is complete, a fluorous tag is introduced into the reaction mixture to selectively "catch" the desired oligosaccharide to form fluorous tagged product, which is isolated from other impurities by fluorous solid phase extraction (F-SPE). Followed by "release" and another "F-SPE", the purification of desired product is achieved. A trisaccharide and a tetrasaccharide are synthesized using this method. Hpearan sulfate proteoglycans (HSPGs), including syndecans and glypicans, are ubiquitous components of mammalian cell surface and extracellular matrix and they play important roles in various biological processes such as cancer development, angiogenesis. viral infection and wound repair. They are composed of heparan sulfate (HS), tetrasaccharide linkage and core protein and increasing evidence shows both HS and core protein can direct the function of HSPGs. To establish structure-activity relationship, it is important to obtain homogeneous HSPGs. However, naturally existing HSPGs are higly heterogeneous and chemical synthesis has never been reported. To address this issue, we chemically synthesized the ectodomain of human syndecan-1. Chapter 3 described an efficient synthetic route which has been established to synthesize a HS bearing glycopeptide. The success of the synthesis will lay the foundation for accessing other proteoglycan structures.
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