透過鈷-媒介的費里爾型重組經由Ｄ-核糖從事前列腺素E2的合成研究

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研究生：	邱皓翔 CHIU, HAO-HSIANG
論文名稱：	透過鈷-媒介的費里爾型重組經由Ｄ-核糖從事前列腺素E2的合成研究 Synthetic Studies on Prostaglandin E2 from D-Ribose by using Cobalt-Mediated Ferrier-type Rearrangement
指導教授：	磯部稔 MINORU ISOBE
口試委員:	汪炳鈞 Uang, Biing-Jiun 鍾文聖 Chung, Wen-Sheng
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：	2012
畢業學年度：	100
語文別：	英文
論文頁數：	171
中文關鍵詞：	前列腺素
外文關鍵詞：	prostaglandin
相關次數：	點閱：2 下載：0
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前列腺素Ｅ2呈現出特別重要的生物活性與特性, 因為其具有影響血液凝結和平滑肌收縮的效用。此外，在分娩或作為輔助子宮頸成熟時，前列腺素E2常用於子宮頸擴張，或是在其它生產的情況下用於誘發子宮收縮。在合成研究裡，我們專注於透過鈷媒介-費里爾類型重組反應來建構環戊酮骨架。而在我們的合成路徑裡，包含：(1) 使用商業上可得到的核糖2當作起始物， (2) 透過C-糖苷化反應3鍵結上炔基以及延伸的長鏈， (3) 並有效地合成出環外烯基的樣品4， (4) 再將炔基部份和八羰基二鈷反應，形成乙炔基鈷錯化合物 5， (5) 更進一步經由費里爾類型重組反應以得到相對應的環戊酮6a-d，其產率介於37～71％。

rostaglandin E2 1 (PGE2) shows important biological activity because of ability to affect blood clotted and smooth muscle contraction. Moreover, prostaglandin E2 1 is used for cervical dilation during parturition or as an adjunct for cervical ripening and to induce uterine contractions in other obstetrical situations. In this synthesis, we focused our attention on constructing the cyclopentanone skeleton of PGE2 through cobalt-mediated Ferrier-type rearrangement. The synthetic routes includes: (1) starting from commercially available D-(-)-ribose 2, (2) carbon chain elongating with acetylenes via C-glycosidation 3, (3) manipulating to exo-vinyl ether 4, (4) converting the acetylenic moiety to its dicobalt complex 5, and (5) implementing Ferrier type rearrangement to afford the cyclopentanones 6a-d in 37-71% yields.

中文摘要………………………I
Abstract………………………II
Acknowledgement……………III
Abbreviatio…………………IV
Contents………………………VI
Figure index………………VIII
Table index…………………IX

Chapter I. Introduction and Research Motif
       I-1. Introduction of Prostaglandins……1
       I-2.  Indroduction of Prostaglandin E2 ..1
       I-3. Total synthesis of Prostaglandin …2
       I-4. Purpose and Research Proposal………8
       I-5. Ferrier-type Rearrangement…………10
        I-5-1. Endocyclic acetal Cleavage……11
        1-5-2. Exocyclic acetal Cleavage Rearrangements..13
        I-5-3. Endocyclic dioxolane and dioxane Cleavage Rearrangements…15
        I-5-4. Acyclic acetal Cleavage Rearrangements……16
        I-5-5. Metal-mediated O->C Rearrangement………17

Chapter II. Results and Discussion
        II-1. Synthesis of C-Glycoside Precursor……21
        II-1-1. Research Motif……………...21
           II-1-2. C-Glycoside Precursor Formation by using Imidate as the Donor…25
           II-1-3. C-Glycoside Precursor formation by C-Glycosidation of Organotrifluoroborate with Glcosyl Flourides…………………………30
       II-2. Cyclopentnone Formation via Ferrier-type Rearrangement………………………33
         II-2-1. Model Studies…………33
         II-2-2. Installation of the C2-Side Chain……38
         II-2-3. Installation of the Desired C3-Side Chain…………46
        II-3. Mechanism of Ferrier-type rearrangement in transition state………54
        II-4. Conclusion…………………55  

Chapter III. Experimental and Reference
         III-1. General…………………………58
         III-2. Experiment Procedure………59
         III-3. Reference……………………89

Appendix…………………………………………92

                                

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