Abstract
This dissertation describes the synthesis of twelve heparin sulfate disaccharides that binds with FGF-1 and the octasaccharide that binds to HSV-1 gD protein. Chapter 1 introduces the cell surface glycoconjugates and explains the biological function of heparin/heparan sulfate. The literature reports about the synthesis of heparan sulfates that bind with FGF-1 and an uncompleted preparation of heparan sulfate octasaccharide that binds with HSV-1 gD protein are summarized in Chapter 2. Chapter 3 describes the retro-synthetic plan of the twelve heparan sulfate disaccharides. Chapter 4 describes the synthesis of twelve heparin sulfate disaccharides that binds with FGF-1. The fully protected disaccharide skeleton was prepared by one-pot glycosylation procedure. The common disaccharide intermediates 213 and 215 were accessed through functional group transformations to form the disaccharide skeleton. With the disaccharide 213 and 215 in hand, the final twelve heparan sulfate disaccharides were synthesized by the subsequent deprotection and sulfonation strategies. Chapter 5 initially introduces the previous work of HSV-1 gD protein binding octasaccharide which was carried out in our research group, followed by the retrosynthesis of our target molecule 276. Chapter 6 describes the construction of heparan sulfate octasaccharide skeleton. The synthetic method was established via changing the sequence of fragment assembly and the leaving group of glycosyl donor. Chapter 7 relates with the synthesis of octasaccharide 276. The octasaccharide skeleton 332 was prepared by assembling glycosyl donor 330, glycosyl acceptor 299 and N,N-diacetyl glycosyl donor 334. Finally, the expected HS target molecule 276, was smoothly obtained from 332 via a series of functional group transformations. The conclusion of our synthetic work is summarized in Chapter 8. A total synthesis of FGF-1 binding twelve heparin sulfate disaccharides and the octasaccharide that binds to HSV-1 gD protein are carried out in an efficient manner. Chapter 9 provides the detailed experimental procedure and physical data of the compounds synthesized herein.