甘露醣的一鍋化選擇性保護及醣鏈結反應的探討

Regioselective One-pot Protection and Glycosylation of D-Mannosides

李佳蓁(Chia-Chen Lee)

指導教授 ： 洪上程

國立清華大學/理學院/化學系/碩士(2007年)

https://doi.org/10.6843/NTHU.2007.00550

摘要

細胞表面的醣共軛分子對於細胞間之訊息傳遞1佔有重要地位，目前已有許多研究表示細胞表面之醣共軛分子與病毒入侵人體或惡性腫瘤增生機制有關，藉由化學合成細胞表面之醣共軛分子可幫助建立生物體內細胞間作用機制。這些細胞表面醣共軛分子是由各種單醣體連接組合而成，例如：葡萄醣(glucose)、艾杜醣(idose)、半乳醣(galactose)、甘露醣(mannose)…等等，單醣體再以不同位置之羥基(hydroxyl group)兩兩相接，並有不同的立體位向選擇性，然而每個單醣分子上都具有多個羥基，所以羥基的選擇與位向的控制是醣化學領域最重要的課題之一。
本篇論文著重於甘露醣的相關研究，專注在位向選擇性一鍋化保護及醣鏈結反應方面的探討。目前關於甘露醣合成的研究仍有一些問題尚待突破，例如：(1) 縮醛保護反應(2,3-縮醛與4,6-縮醛的保護的選擇性)；(2) 2,3-縮醛的立體位向選擇性(exo和endo)；(3) 醣鏈結反應的位向選擇性。本論文利用化合物113為起始物，使用醛類保護基得到2,3和4,6-二縮醛甘露醣115 (產率94%)，並在2,3-縮醛(5環縮醛)中有不錯的位向選擇性(exo/endo = 99/1)，接著進行選擇性開環反應，並結合兩者而成功地發展出一鍋化選擇性保護反應。最後進行醣鏈結反應的研究，得到α位向的甘露醣衍生物。論文中針對縮醛反應的不同條件(例如：溶劑、催化劑、溫度以及試劑當量數的不同)對反應所造成的影響去探討，並說明縮醛產物位向的鑑定方法，還有醣鏈結反應產物的位向鑑定方法。初步研究的結果，相信對未來甘露醣的合成研究有不錯的幫助。

關鍵字

甘露醣 ； 一鍋化

並列摘要

The glycoconjugates outside the cell membrane play an important role in cell-cell interaction as well as cell recognition1. The bio-functions of virus invasion and tumor proliferation are related to the glycoconjugates which have already been revealed in many studies. Chemical synthesis of glycoconjugates can help establish those bio-functions between cells. The glycoconjugates are composed of saccharide units, such as glucose, idose, galactose, mannose … etc. Saccharide units are connected to one another by glycosidic bond formed between the hemiacetal amomeric center of one sugar and the hydroxyl group of another sugar. However, each saccharide contains multiple hydroxyl groups, so the regioselective protection of hydroxyl groups and the stereoselectivity of glycosidic bond would be the biggest challenges of carbohydrate chemistry.
In this thesis, we focus on synthetic chemistry of mannose saccharide unit including one-pot regioselectively protection and deprotection, as well as on glycosylation. There are still some problems which need to be addressed in the synthetic chemistry of mannose, for example: (1) Regioselective formation of acetal protecting groups (the competition among 2,3-acetal formation and the 4,6-acetal formation)；(2) Stereoseletive formation of 2,3-acetal functional groups (the selectivity of exo and endo)；(3) Stereoselective formation of glycosidic bond. In the thesis we use 2,3;4,6-tetrahydroxyl compound 113 as starting material, on acetalization gives 2,3;4,6-dibenzylidene compound 115 94%, The stereoselectivity of the five membered acetal ring is good (exo/endo = 99/1). This dibenzylidene compound was studied for selective acetal ring open reaction. A combination of the two strategies, we successfully developed the one-pot regioselective protection method of mannosides. Finally we studied glycosylation as well, and got α mannosides. The reaction condition including the reagents, catalysts, solvents, and temperature will be discussed in detail, and the identification of stereochemistry of dibenzylidene compound and glycosylation product will be discussed subsequently. We believe our preliminary result can avail synthetic chemistry of mannose in the future.

並列關鍵字

mannose ； one-pot

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