從葡萄糖胺及抗壞血酸合理設計合成細菌特有單醣:偽胺基酸

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林運旺(Yun-Wang Lin) 查詢紙本館藏

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化學學系

論文名稱

從葡萄糖胺及抗壞血酸合理設計合成細菌特有單醣:偽胺基酸
(Rational Design and Synthesis of Bacterial Specific Monosaccharide: Pseudaminic Acid from D-Glucosamine and L-Ascorbic Acid)

★ 二價銅促進1,2,3-三嗪與二級胺之親核性加成氧化反應

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至系統瀏覽論文 (2025-7-21以後開放)

摘要(中)

Pseudaminic acid是一種唾液酸的衍生物，也是許多革蘭氏陰性菌細胞表面的醣聚合物的成分之一。不同革蘭氏陰性菌的細胞表面，有些含有pseudaminic acid，有些則是含有pseudaminic acid的衍生物，而衍生物就是原本pseudaminic acid的架構在碳五或碳七的胺基上做不同的官能基改變。許多研究指出pseudaminic acid與細菌是否能感染宿主細胞因而致病有關，而常見的革蘭氏陰性菌例如:大腸桿菌、弧菌、綠膿桿菌…等。這些革蘭氏陰性菌都具有致病性，並且對人體有害，而大多數的抗生素都不能有效抑制此類細菌，所以對於pseudaminic acid在感染宿主機制上所扮演的角色的研究是非常重要的，但由於目前無法藉由培養細菌大量純化取得pseudaminic acid，因此如何以人工合成pseudaminic acid便顯得十分重要，有鑑於現行發表的數種合成方法有著低總產率及步驟繁複等缺點。在本論文中，我們設計了新的合成路徑，除了能使用較便宜的D-glucosamine和L-ascorbic acid (俗稱維他命C)作為起始物，還能在較少合成的步驟中能將pseudaminic acid的碳五與碳七位置上的疊氮選擇以不同官能基去修飾，形成不同胺的官能基，這對於在pseudaminic acid及相關衍生物的合成是尤為重要的。

摘要(英)

The nonulosonic acid class of sugars consists of 9-carbon α-keto acid carbohydrate monomers. Unique to bacterial species are the recently identified sialic acid derivatives, which are an important sub-class of nonulosonic acids. Pseudaminic acid and legionaminic acid occur as several derivatives with changes in the nature of the amide groups attached to C-5 and C-7. Pseudaminic acid with the L-glycero-L-manno configuration differs from sialic acid in configuration at both the C-5 and C-7 positions in addition to the deoxygenation at C-9 and the N for O substitution at C-7. Pseudaminic acid is found coating the surface of various bacterial human pathogens. Protein glycosylation is an essential post-translational modification in bacteria that has emerged as a new entry to study bacterial pathogenesis and develop novel therapeutic intervention. In particular, Pseudaminylation of proteins has been the subject of significant interest owing to their importance in Gram-negative bacterial pathogens. To date, several synthetic routes have been reported to synthesize pseudaminic acid and its derivatives. All these efforts resulted in poor overall yield and low stereo- and regioselectivity through a number of steps total synthesis. Herein we present two facile de novo synthetic routes toward pseudaminic acid and its functionalized derivatives from easily available D-glucosamine and L-ascorbic acid (vitamin C), respectively. The key reactions in our de novo synthesis involve the diastereoselective azide-based SN2 reaction to create the 2,4-anti-diamino skeleton, followed by the reduction and aldol-type allylation.

關鍵字(中)

★ 革蘭氏陰性菌
★ 醣聚合物

關鍵字(英)

★ Pseudaminic acid
★ nonulosonic acid

論文目次

摘要 i
Abstract ii
誌謝 iii
目錄 iv
圖目錄 vi
表目錄 ix
縮寫表 x
第一章、緒論 1
1-1前言 1
1-2革蘭氏陰性菌 2
1-3對抗革蘭氏陰性菌之抗生素 4
1-4對抗革蘭氏陰性菌之新興療法-醣複合式疫苗 5
1-5 nonulosonic acid 6
1-6 legionaminic acid的高效率合成途徑 9
1-7合成pseudaminic acid的五種不同化學合成途徑 10
1-8研究動機 17
第二章、實驗結果與討論 18
2-1以D-glucosamine hydrochloride作為起始物合成pseudaminic acid的合成路徑 18
2-2以D-glucosamine hydrochloride作為起始物合成pseudaminic acid 的合成詳細步驟 19
2-3以D-glucosamine hydrochloride作為起始物合成pseudaminic acid的實驗步驟與討論 20
2-4以L-ascorbic acid合成pseudaminic acid的合成路徑 24
2-5 以L-ascorbic acid合成pseudaminic acid的詳細步驟 25
2-6以L-ascorbic acid合成pseudaminic acid的實驗步驟與討論 26
第三章、結論 36
第四章、實驗部分 39
4-1實驗儀器 39
4-2合成步驟與光譜資料 40
參考文獻 56
附錄 60

參考文獻

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指導教授

謝俊結侯敦仁

審核日期

2020-7-30

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