臺灣博碩士論文加值系統

本篇論文的主要工作，是開發兩種用於醣類分子羥基的新型正交性保護基，分別為4-Acetoxybenzyl Carbonate (ABC) 和2-(Acetylsulfanyl)methyl Benzoate (ASMB)，以及選擇性去保護。本研究中，是利用三氟甲烷磺酸鐿在甲醇的溶劑下，催化轉酯化反應而達到選擇性去保護之目的。在研究過程中，我們分別將兩者引入至不同醣體分子，測試和其他常見保護基之正交性，例如:苯甲醯基(Bz)、Troc、對甲苯甲氧基(PMB)、叔丁基二甲基矽基(TBDMS)、亞苄基(benzylidene)及縮醛(acetal)等，並在此催化條件下成功進行選擇性去保護反應。而ABC脫去原理是先藉由苯環上乙醯基去除，接著引發連續電子轉移而去保護；另外，ASMB的移除則是先去除硫乙醯基後露出硫醇，接著發生分子內環化而脫去。除此之外，這兩個保護基去保護時所使用之催化劑皆為三氟甲烷磺酸鐿，但我們可以藉由加入其他試劑輔助，使兩者在同一醣體上時，具有選擇性去保護之效果。最後，我們分別將此兩個新型正交性保護基應用於三醣體和雙醣體之合成，測試兩者能否在醣基化條件下穩定存在

The concept of orthogonality has become a mainstream for development of building blocks to carbohydrate synthesis. In this work, we developed two new orthogonal protecting groups for carbohydrates, namely 4-Acetoxybenzyl Carbonate (ABC) and 2-(Acetylsulfanyl)methyl Benzoate (ASMB). Both of them can be efficiently installed into different carbohydrate glycosides. Moreover, the two protecting groups can be selectively removed using Ytterbium(III) trifluoromethanesulfonate [Yb(OTf)3] under mild reaction conditions. The ABC group was selectively removed by deprotecting the phenyl acetate group, followed by 1.6-benzyl elimination to disclose the hydroxyl group. While the ASMB group was selectively removed the S-acetyl group of thioacetate to disclose the thiol group, followed by intramolecular cyclization to release the hydroxyl group. Importantly, these two protecting groups could be distinguished to remove by using MgCl2 additive under Yb(OTf)3 catalytic condition. These two new protecting groups were found to be orthogonal with the benzoyl、Troc (2,2,2-trichloroethyl carbonate)、p-methoxybenzyl、tert-butyldimethylsilyl、acetal groups. Finally, the two new orthogonal protecting groups are also investigated their stability under glycosylation conditions.

謝誌 i
摘要 ii
Abstract iii
目錄 iv
圖目錄 vii
表目錄 viii
流程目錄 ix
第一章 前言 1
1-1 緒論 1
1-2 選擇性轉換與正交性轉換介紹 4
1. 可調控穩定性途徑 (modulated lability approach) 4
2. 正交性轉換 (orthogonal transformations) 5
3. 同步轉換 (simultaneous transformations) 6
1-3 新型正交性保護基之簡介 7
1. 輔助裂解 (Assisted cleavage) 7
2. 碳酸酯基 (Carbonate group) 之策略 10
3. 胺甲酸酯基 (Carbamate group) 之策略 12
1-4 研究動機 16
第二章 結果與討論 20
2-1 新型保護基之設計與置入醣類分子之探討 20
2-2 ABC 及ASMB之去保護優化條件探討 21
2-3 醣體單元的製備 24
2-4 醣體單元引入ABC和ASMB保護基之測試 26
2-5 新型正交性保護基於醣體上之去保護探討 29
2-6 選擇性去除ABC和ASMB保護基之探討 30
2-7 ABC、ASMB與其他保護基之正交性探討 33
2-8 ABC保護基於醣基化反應之探討 35
2-9 ASMB保護基於醣基化之探討 39
2-10 反應機構之推測 41
2-11 結論 42
第三章 實驗步驟與光譜數據 44
3-1 General Information: 44
3-2 General Procedures for ABC and ASMB Groups Installation and Deprotection: 45
3-3 Experimental Procedures and Characterization of Compounds: 47
第四章 參考文獻 71
第五章 附錄(NMR光譜 1H、13C、COSY) 76

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