腺苷與香豆素共軛連結化合物之合成與其構形之探討

根據世界衛生組織(WHO)統計，全球大約有1億7千萬人口感染C型肝炎病毒(Hepatitis C Virus, HCV)，台灣亦有92萬人口為C型肝炎病患。然而感染初期病徵是隱伏的，因此病患往往不自覺已罹患C型肝炎，錯失提早治療機會造成日益越發嚴重之肝臟病變。我們希望合成出具有抗C型肝炎病毒效果的化合物，並進一步討論其合成與立體結構。在DMF中，使用pyridine當鹼的條件，於低溫下以adenosine衍生物與6-substituted coumarin carboxylic chlorides進行先加成後消去之偶合反應，可得到目標化合物以adenosine–coumarin連結在一起的共軛化合物。藉由了解分子之結構構形，可利於抗C型肝炎病毒活性數據之解釋，我們利用核磁共振圖譜、紅外線光譜以及分子模擬計算的技術，發現共軛物醯胺鍵上NH的氫原子與coumarin結構中C=O的氧原子之間，其構形在最穩定能量態下，可觀察到分子內氫鍵的形成；不同取代基之共軛化合物，其purine環及coumarin此兩平面基團，其dihedral angle為0.37°–38.25°，有關此分子構形之觀察數據，可提供我們研究此類化合物於抑制C型肝炎病毒作用機制，提供參考依據。

關鍵字

香豆素；腺苷

並列摘要

According to the World Health Organization (WHO) statistics, about 170 million people infected with hepatitis C virus (HCV) worldwide, and in Taiwan is also a population of 920,000 patients with hepatitis C virus. However, the symptoms are latent early, so patients often do not know they have risk of hepatitis C, resulting in more serious liver disease. Our aim is to synthesis the novel compounds which can inhibit the hepatitis C virus. We successfully synthesized the compounds in which adenosine bound together with coumarin moiety, and these compounds can be easily synthesized by using addition-elimination reaction. We used different techniques like 1H NMR, mass spectroscopy, IR spectroscopy and molecular modeling to study the structure and conformation of the compounds. By comparing all the we conclude that the conformation with the thermodynamically most stable form contain intramolecular hydrogen bondings between the NH proton in amide bond and the carbonyl group in coumarin. The angle between puriune and coumarin planes were 0.37°–38.25°. In the future, we will discuss the structure–activity relationship of anti-HCV, the results of these compounds shall help us to understand the mechanism for the inhibition of hepatitis C virus.

並列關鍵字

Adenosine ； Coumarins

參考文獻

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腺苷與香豆素共軛連結化合物之合成與其構形之探討

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