肝素/硫酸乙醯肝素是屬於葡胺巨醣的一種分子，硫酸乙醯肝素分布在細胞表面及胞外纖維組織裡，而肝素為一結構與硫酸乙醯肝素十分類似的葡胺巨醣，只存在在巨細胞及造血細胞，被廣泛的使用作抗血栓藥物；肝素/硫酸乙醯肝素生合成過程是由核蛋白的絲胺酸餘基以b方式鏈結一特定四醣體，再依序交錯以a(1à4)方式連接氮–乙醯基D式葡萄胺醣及b(1à4)方式連接D式葡萄醣酸，D式葡萄醣酸第五號碳的位置亦可被第五號碳異構酶轉變成L式艾杜醣酸，結構可藉由酵素反應加以修正而變化多端，它們在生理學及病理生理學上都傳達了非常多變且重要的角色，像細胞成長、血液凝結、細胞與細胞之間的作用、傷口癒合、發炎及病毒感染等等。
最近的文獻已經廣泛的報導出肝素/硫酸乙醯肝素與蛋白質間的作用關係，而肝素/硫酸乙醯肝素雙醣體與三醣體可與纖維細胞成長因子有效的鍵結更是已被報導了，但是仍然無法有效的了解其生物活性機制，所以爲了徹底的探討它們的關係，我們開發了新的合成策略合成出三醣體的骨架，並利用交錯且不互相干擾的去保護方式合成出192種肝素/硫酸乙醯肝素三醣體。
本論文主要探討肝素/乙醯肝素三醣體的合成研究，包括利用化合物32為起始物藉由一鍋化組合保護可以六步反應及另四步製備出D式葡萄醣衍生物34、35，D式葡萄胺醣衍生物30可由化合物33經由七步的合成而得到，由化合物34及30合成出雙醣體50 (產率71%)，及藉由一鍋化的醣鏈結反應可得三醣體56 (產率69%)，並有效控制醣鏈結反應的立體位向，經由交錯且不互相干擾保護/去保護方式我們相信可以合成出肝素/乙醯肝素三醣體73。

Heparan sulfate (HS) and its structurally related heparin belong to the family of glycosaminoglycans. HS is ubiquitously distributed on the cell surface and in the basement membrane as well as the extracellular matrix, whereas H is found only in mast cells and some hematopoietic cells and is widely used as an anticoagulant drug. Biosynthesis of H/HS involves the formation of an initial glycosaminoglycan chain, comprising of alternating N-acetyl-D-glucosamine (GlcNAc) and D-glucuronic acid (GlcA) jointed by 1,4-linkages. The subunit of D-glucuronic acid can be transformed into L-iduronic acid by C5-epimerase, the structure may be modified through a series of enzymatic reactions resulting in the various N- or O-sulfate patterns. H/HS play important roles in the physiologic and pathophysiologic processes, such as cell growth, blood coagulation, cell-cell interaction, metabolism, inflammatory processes, and virus infection.
Recent studies have revealed the interactions between H/HS with various proteins. For example, the binding of fibroblast growth factor with fibroblast growth factor receptor can be activated by a few chemically synthesized H/HS-related di- and trisaccharides. However, these saccharides are not enough to characterize the detailed molecular properties of their binding complexes since there are 192 possible H/HS trisaccharides. will be fully synthesized through a novel orthogonal protection/deprotection strategy developed by our laboratory.
In this thesis, we plan to use a common trisaccharide building block in combination of a novel orthogonal protection/deprotection strategy to prepare 48 trisaccharides. The other colleagues will use similar concept to synthesize the rest 144 units. The preparation of the D-glucopyranosyl derivatives 34 and 35 from compound 32 can be carried out via one-pot protection strategy in 6 and 4 steps, respectively. The trichloroacetimidate donor 30 can be derived from 33 in 7 steps. Coupling of 30 with 34 afforded the desired disaccharide 50 (71%) as a single a-isomer, which was subjected to assemble with 35 and a linker to yield the linker-attached trisaccharide 56 (69%) in a one-pot manner. We believe that 48 trisaccharides 73 can be efficiently obtained from 56 through a series of orthogonal deprotection, sulfonation, and oxidation.

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