Abstract
This dissertation describes the synthesis of twelve heparan sulfate disaccharides for FGF-1 binding assay and the preparation of four hexasaccharides by one-pot strategy. Chapter 1 introduces the cell surface glycoconjugates and explains the biological function of heparan sulfate. The literature reports for the preparation of oligosaccharide skeletons by stepwise methods or one-pot glycosylation and the synthesis of heparan sulfates that bind with FGF-1 and other proteins are summarized in Chapter 2 and Chapter 3, espectively. Chapter 4 describes the retro-synthetic plan for the twelve heparan sulfate disaccharides. Chapter 5 describes the synthesis of two monosaccharides for generating twelve heparan sulfate disaccharides, including the optimization of 1,6-anhydro-L-idopyranose preparation. In Chapter 6, glycosylation of two prepared monosaccharides was carried out to yield the disaccharide skeleton followed by several functional group transformations to produce the common intermediate 279. The final twelve heparan sulfate disaccharides were synthesized by the subsequent deprotection and sulfonation strategies. Chapter 7 introduces two binding tests between heparan sulfate disaccharides and FGF-1 by ITC and protein crystallization. The information helps us understand the relationship between disaccharides and FGF-1 more than before. Chapter 8 describes the difficulty in synthesizing heparan sulfate oligosaccharides and the reason of using one-pot glycosylation and new relative reactivity value to prepare oligosaccharide skeletons. In Chapter 9, various monosaccharides for measuring new relative reactivity values are synthesized. Based on these values, the relationship between reactivity of glycosyl thiol and leaving group is explained. Chapter 10 describes the retro-synthetic plan for four heparan sulfate hexasaccharides. Chapter 11 relates with the synthesis of four heparan sulfate hexasaccharide skeletons. The preparation of four final hexasaccharides is summarized in Chapter 12. The conclusion of the present synthetic work is summarized in Chapter 13, a total synthesis of twelve heparan sulfate disaccharides and four hexasaccharides. Chapter 14 provides the detailed experimental procedure and physical data of the compounds synthesized herein.