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| 題名: | 合成1,2,4-triazole和pyrazole類衍生物及相關藥理活性之探討研究
Synthesis of 1,2,4-triazole and pyrazole derivatives and biological activity study |
| 作者: | 王麗雅;Li-Ya Wang |
| 貢獻者: | 癌症生物與藥物研發博士學位學程 |
| 關鍵詞: | 1,2,4-triazole和pyrazole類;一鍋化;1,3-dipolar cycloaddition;Hetero-Diels-Alder reaction;one-pot reaction;1,2,4-triazoles;pyrazoles |
| 日期: | 2014-12-15 |
| 上傳時間: | 2015-11-04 17:02:00 (UTC+8) |
| 出版者: | 中國醫藥大學 |
| 摘要: | 本論文主要是探討一鍋化反應之應用於1,3-dipolar cycloaddition及Hetero-Diels-Alder reaction反應，簡易合成出1,2,4-triazoles和pyrazole等衍生物。
論文的第一部分是探討用以one-pot方式將一系列aldehydes, oxime, 和nitrile (imidate)等起始物與hydrazonoyl hydrochlorides進行1,3-dipolar cycloaddition反應，得到相應的1,2,4-triazoles產物。將合成出的1,2,4-triazoles化合物再送測三株腫瘤細胞株(NCI- H226，TW-01和Jurkat)，其中以triazolic環在N-1含有trifluoromethane官能基以及triazolic環的C-5位置所具有的五圓環基團，包括cyclopentyl, 3-furyl, 3-thienyl, 和 2-pyrrolyl等五圓環，對NCI- H226具有的顯著選擇性抑制效果。
本論文的第二部分，是利用封管條件下將maleimides與pyrazoylimines進行one-pot Aza-Diels–Alder反應，得到一系列高產率pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine產物。依據實驗結果，產物的產率與pyrazoylimines上的N,N-disubstitutedamidinyl的取代基團所造成之torsion conformation成正向關係。
第三部分我們使用5-aminopyrazoles 與 ethyl nitrite或sodium nitrite在一鍋反應，得到5-amino-4-hydroxyiminopyrazoles 和 (E)-N1-aryl-3-aryl-4-[(substituted pyrazolyl)diazenyl]pyrazoles相對產物。相關產物皆經光譜構造鑑定，並進一步經X光單晶繞射驗證其結構。針對5-amino-4-hydroxyiminopyrazoles互變異構體的結構，初次被X光單晶繞射儀的加以證實，而非為先前文獻報導的5-amino-4-nitrosopyrazoles結構。
In this dissertation, we focus on one-pot reaction to prepare the derivatives of 1,2,4-triazoles, and pyrazoles through 1,3-dipolar cycloadditions and hetero-Diels-Alder reaction. First, we developed the efficient one-pot reaction via 1,3-dipolar cycloaddition synthesis method by reacting hydrazonoyl hydrochlorides with a series of aldehydes, oxime, imidate or nitrile to give the corresponding 1,2,4-triazoles. Various of reactants such as 1,2,4-triazole comounds, containing trifluoromethyl group on N-1 phenyl group or possessed the five-membered ring groups including cyclopentyl, 3-furyl, 3-thienyl, and 2-pyrrolyl on the C-5 position of the triazolic ring, possessed the significant selective inhibitory activity against NCI-H226 cancer cells.
In the second part of this dissertation, a modified synthetic method of pyrazolo[3,4-b]pyrrolo[3,4-d]pyridines was developed through an Aza-Diels–Alder reaction of pyrazoylimines with maleimides under the sealed tube condition. Based on the controlling study, the yields for Aza-Diels–Alder reaction seemed proportional to the suitable torsion conformation of pyrazoylimine which was modulated by N,N-disubstitutedamidinyl moiety. The versatile sealed tube technique was also proven to promote the yields of in the Aza-Diels–Alder cycloaddition reaction.
5-Amino-4-hydroxyiminopyrazoles and (E)-N1-aryl-3-aryl-4-[(substituted pyrazolyl)diazenyl]pyrazoles were successfully and conveniently synthesized and studied as the corresponding products by treating 5-aminopyrazoles with ethyl nitrite in the third part. All of 5-amino-4-hydroxyiminopyrazole and (E)-N1-aryl-3-aryl-4-[(substituted pyrazolyl)diazenyl]pyrazole compounds were fully identified by spectroscopic methods. Based on the further single-crystal X-ray diffraction study (ORTEP) resonamce 5-amino-4-hydroxyiminopyrazole structure was identified in the first time and presented as opposed to a 5-amino-4-nitrosopyrazoles tautomer. |
| 顯示於類別: | [癌症生物與藥物研發博士學位學程 ] 博碩士論文
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