合成天然物trans-dehydrocrotonin中間體之反應探討

Abstract

trans-dehydrocrotonin (DHC)及其衍生物通常被作為胃黏膜保護劑，但也可用來治療腹瀉、糖尿病和肝臟炎症。在本論文中，我們也順利獲得其中間體並朝著DHC之全合成的目標邁進。合成的方法為使用三級膦當作親核試劑對烯炔上alpha(delta')碳作親核攻擊，經過分子內環化後，獲得gamma-環內酯結構。在這一鍋化的反應下，經由核磁共振儀、紅外線光譜儀、質譜儀及X光單晶繞射分析鑑定其結構後，可得知在此環內酯的alpha碳上與三級膦鍵結產生伊立德的結構。為了提升對這類多組分反應的產率及探討其取代基的影響，嘗試著使用不同的反應條件與改變不同的反應物取代基。一言以蔽之，由於許多的天然物都含有gamma-環內酯為其骨架，因此這類的合成策略將可應用在天然物的合成上。

trans-dehydrocrotonin (DHC) and its derivatives are considered as cytoprotective agent and can treat several illnesses, such as diarrhea, diabetes, and liver inflammation. As a result, we have achieved its intermediates synthesis and are now heading for application in total synthesis of DHC. In this thesis, we used phosphines as nucleophilic reagents to attack □□□'□carbon of ene-ynes, followed by cyclization, to give □-lactones. We obtained □-lactone bearing □-ylide in one pot and characterized them by NMR, IR, MS and X-ray diffraction analyses. To optimize and discuss the effects substituent effects, we study reactions under different conditions and replace different reactants in this multi-component reactions. Such synthetic methodology can be used to synthesize nature products because lots of nature compounds bear □-lactone skeleton.