Synthetic studies toward the Left Segment of Solanoeclepin A

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研究生：	林峰毅
論文名稱：	Synthetic studies toward the Left Segment of Solanoeclepin A
指導教授：	磯部稔 Minoru Isobe
口試委員:	汪炳鈞吳學亮磯部稔
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：	2013
畢業學年度：	101
語文別：	英文
論文頁數：	199
中文關鍵詞：	天然物、全合成
外文關鍵詞：	natural products, total synthesis
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天然物Solanoeclepin A 1，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防治上。本論文專注在Solanoeclepin A 中左半片段四環骨架152 之建構。包含7-氧基雙環[2.2.1]庚烷、六、七員環和六個不對稱中心之架構。

我們實驗室先前利用(S)-(-)-4-甲氧基-α-甲苄胺為掌性輔助基試劑，經由分子內的Diels-Alder 反應建構出左半7-氧基雙環[2.2.1]庚烷的基本骨架。

合成途徑以化合物106 經由七步反應後可得到烯炔化合140。加成產物140 與
Co2(CO)8 進行錯合反應後獲得環化前驅物144，隨後於二甲基氯化鋁催化下進行分子內普林斯羰基-ene 環化反應可得到產物148a，最後脫去鈷試劑後建構出四環之骨架152。

Solanoeclepin A 1 shows significant hatch-stimulating activity for the potato cyst nematodes. In this thesis, we focused on the synthesis of the tetracyclic diene 152,
including 7-oxabicyclo[2.2.1]heptane moiety, six- and seven-membered ring bearing six chiral centers.

The 7-oxabicyclo[2.2.1]heptane moiety was obtained via a diastereoselective IMDA (intramolecular Diels-Alder reaction) strategy by using a chiral auxiliary (S)-(-)-4-methoxy-α-methylbenzylamine as the source for this synthesis.

This synthesis started from 106 and it was converted to enyne 140 in seven steps. After complexation of acetylene 140 with Co2(CO)8, the cyclization precursor 144 was obtained and subjected to intramolecular Prins-Carbonyl-Ene cyclization via Me2AlCl catalysis to yield stereoselective cyclic product 148a. Next, removal of cobalt afforded the tetracyclic diene 152 framework.

Contents
中文摘要...........................................I
Abstract…………………………………………………………………..II
Acknowledgment………………………………………………………..III
Contents…………………………...…………………………………….IV
Figure Index…...……………………………………………………......VI
Table Index…………………………………………………………......VII
Scheme Index……………………………………………………….…VIII
Abbreviations…………………………………………………………...XI
Chapter 1 Introduction and Research Motif…………………………………...1
1.1 General Introduction …………………………………………………..1
1.2 Review of Synthetic Literature……………………..……………….....2
1.2.1 Hiemstra’s group - Synthesis of Solanoeclepin A Left Segment....2
1.2.2 Tanino’s group - Total Synthesis of Solanoeclepin A……4
1.3 Introduction of Nicholas Effect………………………...……………...6
1.3.1 Removal of Cobalt Complex……………………...………………7
1.4 Lewis-Acid-Catalyzed Prins-Carbonyl-Ene Reaction………………8
1.4.1 Prins-Carbonyl-Ene Reaction via Nicholas Stabilization…...…..10
Chapter 2 Results and Discussions……………….……………………………12
2.1 Retrosynthesis 1……………………………………………………...12
2.1.1 γ-Hydroxyester 64 Formation Following Previous Procedure…..13
2.1.2 Carbon-Carbon Bond Formation via Aldol Reaction…..14
2.1.3 Conjugate Enone Formation……………………………………..19
2.1.4 Study on Weinreb Amide Formation…………………...………..27
2.2 New Retro-synthetic Analysis of Solanoeclepin A Left Segment……29
2.2.1 Silyl Ether Formation Following Previous Procedure……29
2.2.2 Synthesize Terminal Acetylene………………………………….30
2.2.3 Study on Enyne Formation………………………………………34
2.2.4 Diketone Formation via Ruthenium Oxidation……………35
2.2.5 Precursor Formation of Propargyl Alcohol…………………37
2.2.6 Precursor Formation of Radical Cyclization Reaction…………..43 
2.3 Synthetic Route of Hexacarbonyl Complexes………….…………….48
2.3.1 Enyne Aldehyde 143 Formation…………………………………49
2.3.2 Seven-membered Ring Cyclization via Lewis Acid Catalysis…..50
2.3.3 Removal Cobalt of Complex via Hydrosilylation……….………53
2.4 Conclusion…………………………………………………………....57
Chapter 3 Experiment and Reference………………………………………….60
3.1 General……………………………………………………………….60
3.2 Experiment Procedure……………………………………………..62
3.3 References..…………………………………………………………123
Appendix……………...……………………………….………………………..125
                                

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