唾液酸是天然存在的2-酮-3-脱氧非酸類的多樣化家族，其中N-乙醯神經氨酸是最普遍存在的一種。含唾液酸的碳水化合物在自然界中廣泛分布，由於其末端位置帶有負电荷，使唾液酸在免疫方面具有許多作用。這些單糖具有促進分子間和细胞間相互作用的潛力，而在细胞表面上表達的唾液酸也涉及許多生理學和病理學通信相關的作用，並且作受體介導的細胞間相互作用，細胞-細胞黏附，及宿主細胞-病原體識别過程的配體。因此，含唾液酸聚糖的合成對於治療的設計是必要的。
在我的論文第2章中，描述了在第一組中神經氨酸酶的活性位點的開發，用於設計和合成與扎那米蘭(zanamivir)相關的含有1,4-二取代1,2,3-三唑之N-醯基衍生物。我們研究了這些衍生物對第1組（H1N1）和第2組（H3N2）的流感病毒的抑制活性，抑制研究顯示其中幾種具有良好抑制能力，且IC50值在奈米等級（2.3至31nM）範圍内。與空腔殘基形成穩定凡德瓦相互作用的取代基在42a抑制中起關鍵作用，研究表示，環己烷取代的三唑環朝向開放形式的第1組NA的活性位點的疏水區域延伸。抑制劑42a擁有很好的活性可歸因於在該區域中的疏水相互作用。我們預期這種分子洞察可能有助於設計針對這些NA的新的選擇性抑制劑，發展出新一代結構獨特的抗流感藥物。
在我的論文第三章中，我們專注於精子結合蛋白的硫酸化和非硫酸化寡唾酸酸鏈的合成。我的主要目標是9-硫酸化衍生物1a的合成，該合成以化合物1b為起始物，首先在(2→5)-Neu5Gc唾液酸苷的9號位置建構硫酸鹽基團，接著與唾液酸-Tn雙糖進行醯胺偶合反應，探討用於合成非硫酸化衍生物（1b）和硫酸化衍生物（1a）的兩種不同的策略。合成策略是以烯丙醇轉化為乙醇酸部分（33）的唾液酸化產物（12）。然後將這兩個結構單元用於按照相似的反應順序合成雙唾液酸苷(31)。對於-(2→6)-唾液酸-Tn雙糖的合成，我們採用化學酶合成法，以ManCbz為起始物做一鍋化反應。以化合物(91)作為受體，使用酵素NmCSS和Pd26ST以54％的產率合成(93)，然後將雙糖結構單元(88)和(95)轉化為四糖(97)，隨後對帶有保護基的四糖進行去保護，完成了目標硫酸化的化合物1a的合成。

Sialic acids are a diverse family of more than 50 naturally occurring 2-keto-3-deoxy-nononic acids, amongst which N-acetylneuraminic acid is the most ubiquitous. Sialic acid-containing carbohydrates is widely distributed in nature. Because of their terminal location and negative charge, sialic acids have numerous roles in many aspects of immunity. These monosaccharides have the potential to contribute intermolecular and intercellular interactions. Sialic acids expressed on cell surfaces involve many physiological and pathological communications, and serve as ligands for receptor mediated intercellular interactions, cell-cell adhesion, host cell-pathogen recognition processes. Therefore, the synthesis of sialic acid-containing glycans is essential for the design of therapeutics.
In my 2nd chapter, we describe the exploitation of the 150-cavity in the active site of group 1 neuraminidase for the design and synthesis of new 1,4-disubstituted 1,2,3 triazole-containing N-acyl derivatives related to zanamivir. We studied the inhibitory activities of these derivatives against influenza virus of group 1 (H1N1) and group 2 (H3N2). The inhibition studies revealed that several of them are good inhibitors, with IC50 values in the low nanomolar (2.3 to 31 nM) range. . Substituents that form stable van der Waals interaction with the 150-cavity residues play crucial roles in NA inhibition as demonstrated by the potency of 42a (H1N1 IC50 = 2.3 nM, and H3N2 IC50 = 2.9 nM). Docking studies indicated that the cyclohexane-substituted triazole ring extended toward the hydrophobic region in the active site of group 1 NA in open form. The high potency observed for inhibitor 42a may be attributable to the highly favorable hydrophobic interactions in this region. We anticipate that this molecular insight may
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contribute to the design of novel selective inhibitors against these NAs, potentially leading to a new generation of structurally unique anti-influenza drugs.
In my third chapter, we focused on the synthesis of the sulfated and non-sulfated oligosialic acid chain of the sperm binding protein. My initial and major focus has been on the synthesis of 9-sulfated derivative 1a. The synthesis is based on the model compound non-sulfated 1b. I have approached this first by installing the sulfate at the 9’-position of the -(2→5)-Neu5Gc disialoside followed by an amide coupling reaction with sialyl-Tn disaccharide. Two different strategies for the synthesis of non-sulfated derivative (1b) and sulfated derivative (1a) were explored. The synthetic strategy is based on the use of allyl alcohol to achieve an exclusive -sialylation product (12) which was transformed into glycolic acid moiety (33). These two building blocks were then used for the synthesis of disialoside 31 following similar sequence of reaction. For the synthesis of (2→6)-sialyl-Tn disaccharide, we followed chemoenzymatic approach starting from ManCbz in an one-pot manner. We employed 91 as an ‘acceptor’ and NmCSS and Pd26ST to synthesize 93 in 54% yield. The disaccharide building blocks 88 and 95 were then transformed tetrasaccharide 97. The subsequent deprotection of this protected tetrasaccharide completed the synthesis of the target sulfated compound 1a.

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