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研究生:黃煒倫
研究生(外文):HUANG, WEI-LUN
論文名稱(外文):One-Pot Organocatalytic Enantioselective Michael-Acetalization-Reduction-Nef Reaction for the Synthesis of Tetrahydrofuro[2,3-b]benzofurans and the Formal Synthesis of Aflatoxin B2
指導教授:洪伯誠
指導教授(外文):HONG, BOR-CHERNG
口試委員:洪伯誠周德璋曾瑞昌
口試委員(外文):HONG, BOR-CHERNGCHOU, TEH-CHANGTSENG, JUI-CHANG
口試日期:2017-01-13
學位類別:碩士
校院名稱:國立中正大學
系所名稱:化學暨生物化學研究所
學門:自然科學學門
學類:化學學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:中文
論文頁數:689
中文關鍵詞:一鍋化合成Michael-acetalization-reduction-Nef 反應黃麴毒素
外文關鍵詞:One-Pot SynthesisMichael-acetalization-reduction-Nef reactionAflatoxin B2
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本論文合成一系列具有tetrahydrofuro[2,3-b]benzofuran 骨架之化合物。主要的方法是利用一系列的反式-2-(2-硝基乙烯基)苯酚與醛類化合物進行連續性不對稱有機催化Michael-acetalization-reduction-Nef 反應,以及一鍋化合成的策略來合成具有tetrahydrofuro[2,3-b]benzofuran 骨架之化合物。此一鍋化反應具有高產率和高鏡像選擇性,可作為高效合成tetrahydrofuro[2,3-b]benzofran 類化合物的方法。本研究利用此方法並成功合成出dihydro aflatoxin D2 (11),達成aflatoxin B2 之形式全合成。此外,並藉由X-ray 單晶繞射分析本研究所合成之前驅物(-)-11 與化合物(±)-98以及內酯化合物(+)-105,確認其結構及其絕對組態。
The sequential asymmetric organocatalytic Michael-acetalizationreduction-
Nef reaction of (E)-2-(2-nitroethenyl)phenols and aldehydes through
one-pot strategy for the enantioselective synthesis of tetrahydrofuro[2,3-
b]benzofuran derivatives with good yields and high enantioselectivities was
accomplished. This one-pot reaction method provides an efficient way for the
synthesis of dihydro aflatoxin D2 (11), which constitutes a formal total
synthesis of aflatoxin B2. In addition, the structure and absolute configurations
of tetrahydrofuro[2,3-b]benzofuran derivatives were confirmed by X-ray
crystallographic analyses of their single crystals.
目錄
謝誌 ..................................................................... I
摘要 ................................................................... III
Abstract................................................................. IV
縮寫對照表 ............................................................... V
目錄 .................................................................... VI
表目錄 .................................................................. IX
圖目錄 ................................................................... X
附圖目錄 ............................................................... XII
一、緒論 .................................................................. 1
1.1、Tetrahydrofuro[2,3-b]benzofuran 骨架介紹[1] .......................... 1
1.2、文獻回顧 ............................................................. 3
1.2.1、Tetrahydrofuro[2,3-b]benzofuran 衍生物與形式Aflatoxin B2 合成 ....... 3
1.3、Michael-Acetalization-Reduction .................................... 10
1.3.1、Michael-Acetalization ............................................ 10
1.3.2、Michael-Acetalization-Reduction .................................. 12
1.4、Nef 反應 ............................................................ 13
1.5、研究動機 ............................................................ 19
二、結果與討論 ........................................................... 20
2.1、製備2-(3-羥基-2-甲基-1-硝基甲烷)苯酚(49) .............................. 20
2.2、Nef 反應條件篩選 .................................................... 21
2.3、一鍋化方法Michael-Acetalization-Reduction-Nef 反應合成衍生物 .......... 24
2.4 合成Tetrahydrofuro[2,3-b]benzofuran 化合物35 ......................... 30
2.5 化合物110 與乙醛進行Michael 反應催化劑條件篩選 .......................... 34
2.6、由乙醛一鍋化合成Tetrahydrofuro[2,3-b]benzofuran 骨架衍生物 ............ 36
2.7、Aflatoxin B2 前驅物11 之形式合成 ..................................... 46
2.7.1、Aflatoxin B2 前驅物11 之形式合成(合成規劃一) ........................ 46
2.7.2、Aflatoxin B2 前驅物11 之形式合成(合成規劃二) ........................ 54
2.7.3、Aflatoxin B2 前驅物11 之形式合成(合成規劃三) ........................ 64
2.8、結構鑑定 ............................................................ 67
2.8.1、化合物98 之NMR 光譜分析 ............................................ 67
2.9、反應機構之推導 ....................................................... 72
2.9.1、一鍋化Michael-Acetalization-Reduction-Nef 反應之反應機構 ........... 72
2.9.2、形成內酯化合物105 之反應機構 ........................................ 76
三、結論 ................................................................. 77
四、實驗與光譜數據 ........................................................ 78
4.1、實驗儀器 ............................................................ 78
4.2、製備2-(3-羥基-2-甲基-1-硝基甲烷)苯酚(49) .............................. 80
4.3、Nef 反應條件篩選實驗步驟(表二) ........................................ 82
4.4 起始物製備 ........................................................... 84
4.5 一鍋化方法Michael-Acetalization-Reduction-Nef 反應合成衍生物 ........... 92
4.6、乙醛進行Michael-Acetalization-Reduction 條件篩選之實驗步驟(表四) ...... 142
4.7、Michael 反應催化劑條件篩選之實驗步驟(表五) ............................ 147
4.8、化合物35 之合成步驟 ................................................. 149
4.8.1、由化合物110 合成化合物35 .......................................... 151
4.8.2、由化合物110 一鍋化合化合物35 (表六) ................................ 154
4.8.3、反式-2-(2-硝基乙烯)苯酚一鍋化合成化合物35 (表七) .................... 156
4.9、合成前驅物11 (合成規劃一) ........................................... 159
4.9.1、化合物104 之酸性條件去保護試驗(表十) ................................ 159
4.9.2、由化合物121 到前驅物11 ............................................ 161
4.9.3、以化合物122 合成前驅物11 (表十一) .................................. 163
4.10、合成前驅物11 (合成規劃二) .......................................... 164
4.10.1、2,4,6-三羥基苯甲醛選擇性甲基化試驗(表十二) ......................... 168
4.10.2、由化合物138 與139 製備143 與144 .................................. 170
4.10.3、一鍋化合成化合物127 與化合物147 ................................... 177
4.11 合成前驅物11 (合成規劃三) ........................................... 187
五、參考文獻 ............................................................ 199
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