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研究生:林子平
研究生(外文):Zi-Ping Lin
論文名稱:利用共軛的endo-Glycals經由Michael加成反應合成α-2-Deoxy-ulosides及β-Enaminals的衍生物
論文名稱(外文):Synthesis of α-2-Deoxy-ulosides and β-Enaminals Derivatives by Michael Addition of Conjugated endo-Glycals
指導教授:林煇章
學位類別:博士
校院名稱:中國醫藥大學
系所名稱:藥物化學研究所博士班
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:中文
論文頁數:198
中文關鍵詞:氮醣醣加成
外文關鍵詞:α-2-Deoxyulosidesβ-EnaminalsMichael addition
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Hex-1-en-3-ones與多種含氧的親核試劑,在氫氧化鈉的條件下於室溫反應30分鐘,可得到 Michael 加成產物α-2-deoxyulosides,此醣加成產物具有高產率及高的立體選擇性。此外,改用含硫的親核試劑進行反應時,在0℃的條件下反應90分鐘,也可順利得到高產率及高立體選擇性的α-2-deoxyulosides。
利用C-2-Formylglycals與一級胺進行Michael加成反應,可順利得到高產率的β-enaminals,隨後用NaBH4及醋酸為溶劑的條件下,卻非預期的對allyl ether進行了還原性裂解反應,可得到一致性的3-deoxy-β-enaminals。β-enaminals在鋅粉及醋酸為溶劑的條件下,會進行四號脫氫,可得到雙烯化合物。此現象歸因於形成亞胺離子態中間體及不同的還原能力所致。

α-2-Deoxyulosides were synthesized in moderate to good yields by Michael addition of various O-nucleophiles to hex-1-en-3-ones in the presence of NaOH. These glycosyl additions were complete in 30 min at room temperature with high α-stereoselectivity in 53–92% yield. In addition, high α-stereoselectivity was also observed when S-nucleophiles were examined at 0 oC for 90 min.
β-Enaminals were successfully synthesized in good to excellent yields by the reaction of C-2-formylglycals with primary amines. Subsequent reaction with NaBH4 in HOAc led to unexpected reductive cleavage of allyl ether, i.e. the hydrodealkoxylation took place to produce the corresponding 3-deoxy-β-enaminals. In contrast, the reaction of β-enaminals with Zn/HOAc performed H4-elimination to afford a diene product. The result was attributed to the formation of a common eneiminium ion intermediate, and the different reduction reactivity.

目錄……….…………………………………………………………………...I
縮寫目錄…………………………...………………………………………..III
圖表目錄…………………………….……………………………………..VII
<第一部分>
中文摘要……………………………...……………………………………...X
英文摘要…………………………………..………………………………XI
第一章 緒論……………………………………………………………1
2-Deoxyglycosides之研究背景……………….…...…….……………1
第二章 研究目的與動機……………………….………………………12
第三章 結果與討論…………………………………………………….13
3.1 Hex-1-en-3-ulose之合成……………………......…...………….13
3.2 路易士鹼及溶媒之優化………………..………………......….…14
3.3 利用醇類、醣醇及硫醇進行醣加成反應…………...……….…16
第四章 結論…………………………………………………...………..28
<第二部分>
中文摘要……………………………...………………………………….XII
英文摘要…………………………………..……………………….……XIII
第一章 緒論……………………………………………………….……30
1.1 Noeuromycin之研究背景………………..………..……...………30
1.2 β-Enaminals之研究背景……..………………………………..…32
1.3 對含氧丙烯基的還原性裂解反應之研究背景…………….……37
第二章 研究目的與動機……………………….………………………45
第三章 結果與討論…………………………………………………….46
3.1 β-enamino aldehydes之合成……...………...………...………..…46
3.2 在NaBH4-HOAc條件下對β-enaminals進行還原反應……...…..51
3.3 在Zn-HOAc條件下對β-enaminals進行還原反應……………..58
3.4 利用β-enamino carbonyl衍生物來開發azasugar之探討…….....61
3.5 未來工作(Future work)……………….……………………….....66
第四章 結論…………………………………………………...………..68
第五章 實驗部分…………………...…………………………………..70
5.1 試藥、溶媒及材料…………………………………………..……70
5.2 重要儀器……..………………………………………………..…75
5.3 化合物的製備………………………………………………..…78
參考文獻……………………………………………………………...……122
附錄(圖譜部分)………………………………………………………….130


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