臺灣博碩士論文加值系統

摘要：
Kynapcins的部分：
Kynapcin-24是由韓國蕈類植物Polyozellus multiflex所萃取分離出來的天然物，其結構上是一種新型的benzofuran二聚合物，在生物活性上，具有抑制serine protease（絲胺酸蛋白分解酵素）的其中一種prolyl endopeptidase（PEP）的活性（kynapcin-24具有IC50 = 1.14 mM的效果），並且對其它的serine protease如chymotrypsin、trypsin及elastase也具有抑制活性，但其效果較不顯著。根據研究報告顯示，Alzheimer（老人痴呆症）症病人身體內PEP的活動量是比正常人高出許多，所以kynapcin-24具有抑制PEP在人體內的活動量，即可有效防止老人痴呆症所引起的記憶喪失和注意力的遲緩。
在kynapcin-24的合成策略上，我們試嘗以benzaldedyde化合物12與diethy 2-bromomalonate或methyl 2-bromoacetate合成benzofuran模型化合物14和化合物16，再來引進benzofuran環C(5)位置上的hydroxy官能基。經過Baeyer-Villiger的氧化反應、Vilsmeier-Haack的formylation、benzofuran的環化反應以及去甲基保謢的反應後，成功的在benzofuran環C(5)位置上引進hydroxy官能基，得到benzofuran化合物8。不過接下來在benzofuran環C(3)位置上引進溴化取代基時，卻無法得到化合物33，只得到在benzofuran環C(4)位置上引進溴化取代基的化合物34，導致無法順利進行Stille偶合反應來合成天然物kynapcin-24。

Sexipyridines的部分：
在1997年，奈米材料分子sexipyridine 3第一次被Kelly T. R.的實驗室合成出來，sexipyridine 3被設成具有D3h軸對稱結構、奈米孔洞大小和2,2-bipyridine多芽配位基的分子。而本文中合成的sexipyridine 5，不僅具備sexipyridine 3的分子特性外，其分子內還具有acetylene長鏈的鍵結，可以使sexipyridines形成更穩定的p電子共振系統，在結構上也可形成更大環的sexipyridines及不同大小的奈米孔洞。而將合成出來的sexipyridines，利用分子自組裝的特性與金屬進行錯合反應，形成三維的聚合網狀超分子化合物，此網狀超分子具有類似沸石的功能，因此我們稱為有機沸石。
在sexipyridine 5的合成策略上，我們以化合物40做為起始物，經過多步的反應後，能順利的得到aldehyde化合物45，再經由Corey-Fuchs的反應得到acetylene化合物39的單體化合物，利用[Cu(OAc)2]2．2H2O作為催化試劑，將acetylene化合物39進行聚合反應得到dipyridine化合物38，再進行Stille偶合反應來得到quarterpyridine化合物50和sexipyridine化合物5。

Abstract：
Kynapcins part：
Kynapcin-24 was isolated from the mushroom Polyozellus multiflex and was a new benzofuran dimer structure. On the biological activation, it had shown to noncompetitively inhibit a serine protease of prolyl endopeptidase (PEP), with an IC50 value of 1.14 mM. Kynapcin-24 was less inhibitory to other serine proteases such as chymotrypsin, trypsin, and elastase. PEP activity of Alzheimer’s patients has been found to be significantly higher than that of the normal person. It has been postulated that specific PEP inhibitors could prevent memory loss and increase attention span in patients suffering from senile dementia.
On the synthetic strategies of kynapcin-24, we tried to synthesize the modle coumpound of benzofuran 14 and 16 with benzadehyde 12 and 2-bromomalonate or methyl 2-bromoacetate. And then came to make the hyhroxy fouction group on the positon of C(5) on benzofuran. After Baeyer-Villiger oxidation, Vilsmeier-Haack formylation and bnezofuran cyclization, we successfully made the hyhroxy fouction group on the positon of C(5) on benzofuran to approach benzofuran 8. But next when made the bromination on the positon of C(3) on benzofuran, it was unable to get compound 33. It olny got the compound 34 bromination on the positon of C(4) on benzofuran. Finally, it is unable to carry on Stille copling reaction to formate kynapcin-24.

Sexipyridines part：
In 1997, sexipyridine 3 was first synthesized by Kelly T. R. laboratory and designed a ligand with D3h symmetry, exploiting the well-documented chelating properties of the 2,2'bipyridine system with a diverse range of metals. It had the potential to form predictable chelated network structures (e.g., organic zeolites). And in the article, we would synthesize the sexipyridine 5. It not only possessed the the molecule characteristic of sexipyridine 3, but also with acetylene long chain was formed in its molecule. It could make sexipyridines form more steady p-electronic resonance system, form large cyclic sexipyridines structure and to change the pore sizeof the network.
On the synthetic strategies of sexipyridine 5, we could smooth to get aldehyde 45, after more than reaction of step by compound 40. And then got the acetylene 39 via Corey-Fuchs reaction and dipyridine 38 was synthesized by [Cu(OAc)2]2．2H2O as catalysis reagent with acetylene 39. Finally, quarterpyridine 50 and sexipyridine 5 could be aproached by Stille coupling reaction with dipyridine 38.

中文摘要..................................................1
英文摘要..................................................3
第一章：緒論..............................................5
1-1 天然物Kynapcin-24.....................................8
1-2 Sexipyridines.........................................9
第二章：實驗部分.........................................14
2-1 一般實驗.............................................14
2-2 鑑定儀器.............................................14
2-3 藥品與溶劑...........................................15
2-4 化合物的鑑定與合成...................................17
2-4.1 Kynapcins化合物的鑑定與合成........................17
2-4.2 Sexipyridines化合物的鑑定與合成....................25
第三章：結果與討論.......................................34
3-1 Kynapcin-24及其衍生物的合成..........................34
3-1.1 Kynapcin-24的回溯合成..............................34
3-1.2 Benzofuran的模型與化合物16的合成...................35
3-1.3 化合物8單體的合成..................................37
3-1.4 Benzofuran 模型C(3)位置上的溴化反應................40
3-1.5 Stille偶合反應.....................................43
3-1.6 Benzofuran化合物25的溴化反應和Stille偶合反應.......45
3-2 Sexipyridines的合成..................................48
3-2.1 Sexipyridine的回溯合成.............................48
3-2.2 2-Bromopyridine-4-carbaldehyde的合成...............51
3-2.3 Corey-Fuchs反應與2-bromo-4-ethynylpyridine的合成...53
3-2.4 Dipyridine化合物38的合成...........................56
3-2.5 Stille偶合反應.....................................57
第四章：結論.............................................62
第五章：參考資料.........................................63
附件一、化合物光譜圖
附件二、已發表文章

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