臺灣博碩士論文加值系統

DSGb5是腎臟癌細胞上重要的腫瘤相關抗原，同時也被發現於肝癌以及前列腺癌，對於癌細胞的增生以及轉移有很高的關聯性，因此了解DSGb5在生物體中所扮演的角色極為重要，然而DSGb5至今仍未發展出有效的合成策略，在取得不易的情況下，關於DSGb5在癌症相關領域的研究仍有很大的限制。
本論文嘗試以實驗室所建立的酵素系統並結合化學合成策略用運用於DSGb5之合成，在此合成策略中，關鍵步驟為以Gb3衍生物受體進行[2+3]醣基化反應，此步驟中同時面臨位向及立體選擇性的問題，因此本論文主要探討將非還原端之半乳糖四號羥基以不同保護基做保護以及嘗試其它反應條件，試圖解決選擇性以及低產率的問題，並搭配使用核磁共振光譜及參照實驗室利用全酵素反應所建構之Gb5，以確認產物結構，目前已成功地合成出Gb5以及釐清以不同Gb3衍生物受體進行[2+3]醣基化反應後所產生之五醣結構。未來將以目前開發出的合成策略有效地合成DSGb5完成。

Disialosyl globopentosylceramide (DSGb5) is a kind of ganglioside, which was isolated from renal cell carcinoma (RCC) tissue extracts. Current studies indicate that DSGb5 of cell surface may involve in the metastatic capability of cancer cells, thereby enhancing cell migration. However, the effective method for the synthesis of DSGb5 has not yet been reported. Development of a new synthetic route to access DSGb5 is an important starting point to study its roles in biological systems.
In this thesis, developed a new strategy to synthesize DSGb5 precursor, Gb 5. The key step in this strategy is [2+3] glycosylation to yield Gb5. The trisaccharide acceptor Gb3 was synthesized by enzymatic method to avoid the drawback of selectivity in chemical synthesis of 1,2-cis glycosidic bond while the disaccharide was prepared by borinic ester assisted glycosylation. Many protected Gb3 acceptors were synthesized and evaluated for their efficiency and selectivity in glycosylation with disaccharide donor. The structure of pentasaccharides were identified by 2D NMR spectrum and comparison of the proton NMR spectra with Gb5 (obtained by enzymatic method) spectum. The protected Gb5 structure was unambiguously determined. Thus, the developed method has paved a route for the future synthesis of DSGb5 by chemoenzymatic strategy.

摘要 I
Abstract II
圖目錄 V
表目錄 VI
流程目錄 VII
縮寫表 VIII
第一章 緒論 1
1-1 結合化學與酵素方法建構醣體 1
1-2 癌細胞相關醣體抗原 2
1-3 腎細胞癌相關抗原─DSGb5 4
1-4唾液酸 6
1-5以酵素建構Galα(1,4)Lac醣苷鍵 7
1-6以酵素建構Siaα(2,3)Gal醣苷鍵 9
1-7唾液酸化學合成方法分析 13
1-8 順式二醇 (cis-diol) 活化試劑 16
1-9研究動機及目的 17
第二章 實驗結果與討論 18
2-1 DSGb5 逆合成分析 18
2-2 雙醣予體5之合成 20
2-3 醣受體8之合成 22
2-3-1 乳糖衍生物9之合成 22
2-3-2 Gb3-OC6H12N3之合成 23
2-3-3 Gb3-OC6H12N3之選擇性保護 24
2-4 唾液酸予體之合成 26
2-5 醣基化反應 27
2-6 結果分析與改善 30
2-6-1與全酵素合成之DSGb5做比較 30
2-6-2 檢視步驟與討論 31
2-7 正確三醣受體之合成 35
2-8 以3-OH, 4-OH三醣受體進行醣基化反應 37
2-9 以3-OH, 4-OAc三醣受體進行醣基化反應 39
2-10 以3-OH, 4-OBn三醣受體進行醣基化反應 42
2-11 未來展望 44
2-12 結論 45
第三章 實驗部分 46
3-1 Reagents and Solvents 46
3-2 Spectra Notes 47
3-3 Synthetic Procedures and Characterization 48
第四章 參考文獻與資料 87

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