Pseudouridine 的合成研究

Abstract

自然界中，C-nucleosides相較於N-nucleosides為少數，N-C醣苷鍵在合成途中有機會被水解以及酵素降解，C-C醣苷鍵能避免掉此種影響。生物體內RNA核醣核酸以及DNA去氧核醣核酸皆是N-nucleosides。在此，我們團隊感興趣的核苷為pseudouridine (Ψ)，於1951年從t-RNA被發現，是第一個也是最大量的C-nucleosides，相較於uridine (U) 多出了一個氫鍵，增加RNA的剛性及穩定性。然而建構C-C醣苷鍵難度難度較高，控制產物的立體組態也是一大挑戰，在此，我們對建立醣苷鍵進行了多種方法的研究，希望能有效的控制立體組態，合成pseudouridine。In nature, N-nucleosides outnumber C-nucleosides. N-C glycosidic bonds can undergo hydrolysis and enzymatic degradation during synthesis, whereas C-C glycosidic bonds can avoid such effects. Both RNA (ribonucleic acid) and DNA (deoxyribonucleic acid) in organisms consist of N-nucleosides. The focus of our team lies on a particular nucleoside called pseudouridine (Ψ), which was first discovered in t-RNA in 1951. pseudouridine is the first and most abundant C-nucleoside. In comparison to uridine (U), it forms an additional hydrogen bond, enhancing the rigidity and stability of RNA. However, constructing C-C glycosidic bonds is challenging, and controlling the configuration of the product during synthesis presents a major obstacle. Consequently, we have employed various methods to establish glycosidic bonds with the aim of effectively controlling the configuration and synthesizing pseudouridine.