具有神經再生活性的神經節苷脂Hp-s1、DSG-A與類似物的全合成研究

Total Synthesis of Ganglioside Hp-s1, DSG-A and their Analogus Possessing Neuritogenic Activity

迦納辛(Ganesh Shelke) ； 楊世安(Shih-An Yang) ； 葉俊鴻(Chun-Hong Yeh) ； 戴弘儒(Hung-Ju Tai) ； 林秋雅(Chiu-Ya Lin) ； 廖盈茹(Ying-Ju Liao) ； 酈又瑄(Yu-Hsuan Lih) ； 陳宛欣(Wan-Shin Chen) ； 羅順原(Shun-Yuan Luo)

《化學》 74卷2期 (2016/06) Pp. 115-129

https://doi.org/10.6623/chem.2016010

摘要

神經節苷脂Hp-s1與DSG-A是由刺冠海膽的卵巢中單離出來。這些分子以Neu5Ac α2→6Glc β1→1Cer的結構組裝而成，並且顯示出獨特的神經再生活性。直至今日，已有大量神經節苷脂由海洋動物中單離得到，但僅有少數幾個具有臨床的潛力。神經節苷脂Hp-s1與DSG-A具有神經再生的活性，因此化學家有興趣於開發方法以合成這些分子。由最近的期刊中，我們可以歸納出脂肪酸的碳鏈與神經醯胺會影響到神經節苷脂的神經再生活性。植物鞘胺醇的合成可藉由使用市售的D-來蘇醣作為起始物而得到。藉由廣泛的研究可利用各式的醣受體與醣予體例如亞胺酸酯、醣基碘化物、STol、STaz、SBox、鹵素、乙醯基等以得到懸殊比例的立體異構物。溶劑、促進劑及反應溫度也會影響產物的比例。有趣的是，在醣鏈結反應中，具有噁唑烷酮的唾液酸醣予體可以獲得絕對的α-異構物。蔡祐輔教授發表了神經節苷脂DSG-A的首篇全合成，是利用化學選擇性醣鏈結及一個[1 + 1 + 2]的合成策略。而神經節苷脂Hp-s1 1與它的衍生物(1b-1k)目前已被本實驗室合成出來。

關鍵字

神經節苷脂 ； D-來蘇醣

並列摘要

Ganglioside Hp-s1 and DSG-A were isolated from the ovary of sea urchin Diadema setosum. These are assembled as Neu5Acα2 → 6Glcβ1 → 1Cer linkage and shows neuritogenic activity. Large number of gangliosides are isolated till date from marine animal but only few of them has clinical potential. Ganglioside Hp-s1 and DSG-A possess an neuritogenic activity and hence chemists are interested to develop a method to synthesize these molecules. From the recent studies, we can conclude that fatty acid chain length or ceramide moiety can affect neuritogenic activity of gangliosides. Phytosphingosine synthesis was also achived by using commercially available Dlyxose as starting material. Extensive research was carried out to achive specific (α:β) ratio by using various substituents on acceptor and donors such as imidate, STol, STaz, SBox, Halo, OAc etc. Solvent, promotor and reaction temperature are also influence the product ratio. Interestingly, oxazolidinone sialic acid donor gives exclusive α isomer in glycosylation reaction. The Tsai et al. published a first total synthesis of monomethylated ganglioside, DSG-A via chemoselective glycosylation and a [1 + 1 + 2] synthetic strategy. Ganglioside Hp-s1 1 and its analogus (1b - 1k) was synthesized by our laboratory.

並列關鍵字

Ganglioside ； Hp-s1 ； DSG-A ； PC-12 ； D-lyxose