藉由鈀催化Heck醣苷化反應進行Pseudouridine的合成研究
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2016
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Abstract
C-nucleosides相較於N-nucleosides擁有較穩定的醣苷鍵，在醫藥化學及生物化學上具有應用的潛力。且在自然界中，存在許多C-nucleosides的天然物，具有多樣的生物活性，其中天然物pseudouridine及其衍生物2’-deoxypseudouridine為我們有興趣的化合物。本研究主要著重於利用Heck反應將醣體和具有碘取代的芳香及雜環化合物進行耦合，形成新的碳-碳醣苷鍵。改變以往需要使用到有毒且而昂貴的AsPh3作為配體，以雙芽基配體作為配體進行反應，發現也有很好的區位及立體選擇性。並將研究結果應用於2’-deoxypseudouridine及pseudouridine的合成。
The nucleosidic bond of C-nucleosides are much more stable than N-nucleosides, which allows potential applications of C-nucleosides in medi-cinal chemistry and chemical biology. Some of the naturally occurring C-nucleosides possess a wide variety of biological activities. We are particu-larly interested in the synthesis of pseudouridine and 2’-deoxypseudouridine. In this thesis, we employed Heck-type coupling reactions to form C-C bonds between the anomeric carbon of 1, 2-unhydrous sugar derivatives and aryl iodides or iodo-heterocycles. Instead of utilizing toxic and expensive AsPh3 as the ligand, tour study has showed that the use of bidentate ligands for Heck-type coupling reactions were highly regio- and stereoselective. The methodology is applicable to the synthesis of 2’-deoxypseudouridine and pseudouridine.
The nucleosidic bond of C-nucleosides are much more stable than N-nucleosides, which allows potential applications of C-nucleosides in medi-cinal chemistry and chemical biology. Some of the naturally occurring C-nucleosides possess a wide variety of biological activities. We are particu-larly interested in the synthesis of pseudouridine and 2’-deoxypseudouridine. In this thesis, we employed Heck-type coupling reactions to form C-C bonds between the anomeric carbon of 1, 2-unhydrous sugar derivatives and aryl iodides or iodo-heterocycles. Instead of utilizing toxic and expensive AsPh3 as the ligand, tour study has showed that the use of bidentate ligands for Heck-type coupling reactions were highly regio- and stereoselective. The methodology is applicable to the synthesis of 2’-deoxypseudouridine and pseudouridine.
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C-核苷, 類尿嘧啶, 2’-脫氧類尿嘧啶, Heck反應, C-nucleosidee, pseudouridin, 2’-deoxypseudouridine, Heck reaction