以砜基為連結元件的固相有機合成及化合物庫之合成研究

Abstract

摘要 在本論文中，我們以砜基樹酯為固相有機合成之載體，並開發三甲基鋁為產物之切割試劑，成功的合成出結構骨架類似化合物Ⅰ及化合物Ⅱ之小型化合物庫。 首先，在液相反應中我們以benzene sulfinic acid sodium salt為起始物，經歷六個反應步驟，得到化合物7，總產率約為15 %，並確認合成結構骨架類似化合物Ⅰ及化合物Ⅱ之反應流程的可行性。 接著，我們在實驗室成功的製備以砜基為連結元件之樹酯8；應用此砜基樹酯8為固相有機合成之載體，經由類似液相反應所建立之合成反應條件。最後，並以三甲基鋁為切割試劑，順利將產物由固相載體中釋放出來；應用此固相有機合成技術，我們成功的合成了化合物16、18、21、26、28、31、33、38、41、46及48等11個具有類似結構骨架之化合物庫。 未來希望在國內學術界找到合適的合作對象，測試這些化合物是否具有藥物活性。

化合物I 化合物Ⅱ

Abstract

Using sulfinate functionalized resin as a solid support, we have developed a new cleavage reagent, Al(CH3)3, and successfully synthesized a small library of compounds with structures like compound Ⅰ and Ⅱ. First of all, benzene sulfinic acid sodium salt was used as starting material in liquid phase experiment. Through six reaction steps, we obtained compound 7 in about 15% total yield, which demonstrated that compounds similar to Ⅰ and Ⅱ can be synthesized. Then, we successfully prepared resin 8 which has sulfone linker. Using resin 8 as solid support in SPOS, similar reaction conditions in liquid phase and Al(CH3)3 as cleavage reagent, we obtained the products form solid support. Application of SPOS technique, we synthesized a library of compounds which includes 16, 18, 21, 26, 28, 31, 33, 38, 41, 46 and 48. In the future, we hope to search a cooperative group in the academia to test the potential bioactivity of these compounds.

Compound I Compound Ⅱ