Stereoselective Synthesis of 7-Oxabicyclo[2.2.1]heptanes toward Natural Products, Gibberellic Acid (GA3) and Solanoeclepin A

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研究生：	江景得 Chiang, Ching-Te
論文名稱：	Stereoselective Synthesis of 7-Oxabicyclo[2.2.1]heptanes toward Natural Products, Gibberellic Acid (GA3) and Solanoeclepin A
指導教授：	磯部稔 Minoru Isobe
口試委員:	汪炳鈞 Uang, Biing-Jiun 廖俊臣 Liao, Chun-Chen
學位類別：	碩士 Master
系所名稱：	理學院 - 化學系 Department of Chemistry
論文出版年：	2011
畢業學年度：	99
語文別：	英文
論文頁數：	135
中文關鍵詞：	7-氧基雙環[2.2.1]庚烷、鋅錯合物、分子內狄爾士-阿得關環反應、內酯化反應
外文關鍵詞：	7-oxabicyclo[2.2.1]heptanes, zincates, intramolecular Diels-Alder cycloaddition, intramolecular lactonization
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中文摘要

　　7-氧基雙環[2.2.1]庚烷的衍生物大多具有生物活性，往往在自然界中扮演著重要的角色。在本論文中，我們以此類化合物為主要骨架，應用於天然物的不對稱合成上，如gibberellic acid (GA3) 和 solanoeclepin A。

　　Gibberellic acid (GA3)是一種調節植物生長的賀爾蒙。其可利用7-氧基雙環[2.2.1]庚烷與鋅錯合物(zincate, Me3ZnLi)試劑進行甲基化反應，得到動力學上的加成產物。更進一步在路易士酸的催化下，經由分子內的內酯化反應以完成左半邊的合成。　

　　另一天然物solanoeclepin A，研究發現其具有刺激馬鈴薯中的囊腫線蟲提早孵化的功能，可運用在農業病蟲害的防治上。其主要合成策略是以(S)-(−)-4-甲氧基-α-甲苄胺為掌性輔助基試劑，經由分子內Diels-Alder反應建構出左半邊7-氧基雙環[2.2.1]庚烷的基本骨架。

Abstract

Derivatives of 7-oxabicyclo[2.2.1]heptanes perform an important role in nature, many of which show biological activities. Herein, these skeletons were employed toward stereoselective synthesis of natural products, gibberellic acid (GA3) and solanoeclepin A.

We focused the left hand segment of gibberellinc acid (GA3), which functions as plant growth regulator. The key steps include: (1) the methylation with “zincate”, Me3ZnLi, reagent to give the conjugate adduct without ring-opening of oxa-bridged, and (2) an intramolecular lactonization with Lewis acid to form the lactone.

In addition, an asymmetric synthesis is also described on the oxa- bicyclo[2.2.1]heptane segment of solanoeclepin A, which shows significant hatch-stimulating activity for the potato cyst nematode. The oxabicyclo framework was constructed through an intramolecular Diels-Alder cycloaddition by treatment with the (S)-(−)-4-methoxy-α- methylbenzylamine as well as the chiral auxiliary.

Contents

中文摘要.........................................................I
Abstract..................................................II
Acknowledgment...........................................III
Abbreviations.............................................IV
Contents...................................................V
Figure index.............................................VII
Table index.............................................VIII

Chapter I. Introduction

I-1. Introduction of 7-Oxabicyclo[2.2.1]heptanes...........1
    I-1-1. Synthesis of 7-Oxabicyclo[2.2.1]heptanes........1
    I-1-2. Natural 7-Oxabicyclo[2.2.1]heptanes and
                                     Bioactive Analogues...2
I-2. Introduction and Synthetic Strategy of Gibberellic
                                                   Acid....6
    I-2-1. Introduction of Gibbrellic Acid................6
    I-2-2. Synthetic Strategy of Gibberellic Acid (GA3)....7
I-3. Organozinc Mediated Reactions.........................8
    I-3-1. Organozinc Reagent, RCu(CN)ZnI..................8
    I-3-2. Ate Complexes and Organozincate Reagent,
                                           Me3ZnLi.........9
    I-3-3. The Applications of Organozincate Reagent,
                                           Me3ZnLi........10
I-4. Introduction and Synthetic Strategy of
                                 Solanoeclepin A..........11
    I-4-1. Introduction of Solanoeclepin A................11
    I-4-2. Synthetic Strategy of Solanoeclepin A..........12
I-5. Intramolecular Diels-Alder Cycloaddition of Furan....13
    I-5-1. Literature Review of IMDA Cycloaddition of
                                              Furan.......13
    I-5-2. Synthetic Applications of IMDA Cycloaddition of
                                              Furan.......15

Chapter II. Result and Discussion

II-1. Synthesis of Left Hand Side of Gibberellic Acid
                                               (GA3)......17
    II-1-1. Research Motif................................17
    II-1-2. Synthetic Route...............................18
    II-1-3. Methylation of 7-Oxabicyclo[2.2.1]hepta-2,5-
            diene 21 with Organozincate Me3ZnLi...........19
    II-1-4. The Reactivity of 7-Oxanorbornadiene 21 with
            Organozinc and Organoaluminium Reagents......24
    II-1-5. Lactone Formation Activate by Lewis Acid....27
II-2. Synthesis of Left Hand Side of Solanoeclepin A......35
    II-2-1. Research Motif of Asymmetric 7-
                                    Oxanorbornadienes.....35
    II-2-2. Synthetic Route of Solanoeclepin A............36
    II-2-3. 7-Oxabicyclo[2.2.1]heptene 93 Formation via
                                  IMDA Cycloaddition......37
    II-2-4. Reduction of the Diels-Alder Cycloadduct 93...40
    II-2-5. Formation of γ-Lactam 104 and Further
                                          Synthesis.......42
II-3. Conclusion..........................................44

Chapter III. Experimental and Reference

III-1. General............................................47
III-2. Experimental Procedure.............................49
III-3. Reference..........................................70

Appendix..................................................75

                                

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