請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/90551
標題: (1) Concise Synthesis of Ganglioside Hp-s1 Neu5Ac alpha(2 → 6)Glc alpha(1 → 1)Cer Analogue (2) Preparation of Sphingosine Derivative
(1) 簡潔合成醣苷神經鞘胺脂質Hp-s1衍生物 (2) 製備鞘氨醇衍生物
作者: 戴弘儒
Hung-Ju Tai
關鍵字: ganglioside Hp-s1
sphingosine
醣苷神經鞘胺脂質
鞘胺醇
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摘要: The synthesis of the ganglioside Hp-s1 analogue by changing the stereochemistry at C-1 position of glucosyl moiety is presented. In order to explore the exact stereochemical role of C-1 position of glucosyl moiety, we synthesized ganglioside analogue having alpha-alpha/alpha-beta configuration from non-reducing to reducing end. The characteristic sequence of the glycolipid part was efficiently assembled by coupling of a highly active benzyl protected glucosyl donor and a phytosphingosine derived acceptor with good -stereoselectivity. The corresponding glycolipid acceptor was directly glycosidated with the acetyl-protected sialyl donor part to afford the disaccharide in high yield and stereoselectivity. After amidization formation and global deprotection, ganglioside Hp-s1 analogue (2b) was obtained. Synthesis of phthaloyl protected sphingosine derivative was achieved from commercially available phytosphingosine. In order to increase reactivity of primary hydroxyl group for further glycosylation, the unfavourable hydrogen bonding between primary hydroxyl group with amino group was replaced by installing phthaloyl protected group at N-H position. The reaction sequence as follows: Phthaloyl protection at N-H, benzylidene insertion at C-1 and C-3, iodination at C-4, elimination of iodide and deportection provided the protected sphingosine derivative.
第一部份先透過改變葡萄醣醣鏈結的立體位向,合成出醣苷神經鞘胺脂質Hp-s1的衍生物,其立體化學為葡萄醣體在C-1位置為alpha的Hp-s1衍生物。關於其建構基石,我們先透過具有良好反應性之苄基保護的葡萄醣與植物神經鞘胺醇衍生物進行醣鏈結,形成良好選擇性的醣脂質。接著再將醣脂質與唾液酸衍生物進行醣鏈結,形成雙醣醣脂質化合物,然後透過醯胺化反應形成醯胺鍵,再將保護基都去除,即可得到目標產物Hp-s1衍生物(2b)。 第二部分則從植物神經鞘胺醇為起始物,合成酞醯基保護的鞘氨醇衍生物(117),其中酞醯基保護基上的氧可與一號位置上形成氫鍵,進而增加醣鏈結的反應性。反應步驟如下:先將氮做上酞醯基保護,接著將一號及三號位置的二元醇上亞芐基縮醛保護,然後在四號位置的羥基置換成易離去基之碘後再進行脫碘去形成雙鍵。最後再將亞芐基縮醛保護去掉得到酞醯基保護的鞘氨醇衍生物(117)。
URI: http://hdl.handle.net/11455/90551
文章公開時間: 2018-08-12
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