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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 柳玗珍 | zh_TW |
| dc.contributor.advisor | Woo-Jin Yoo | en |
| dc.contributor.author | 盧彥廷 | zh_TW |
| dc.contributor.author | Yen-Ting Lu | en |
| dc.date.accessioned | 2024-02-22T16:15:48Z | - |
| dc.date.available | 2024-02-23 | - |
| dc.date.copyright | 2024-02-22 | - |
| dc.date.issued | 2023 | - |
| dc.date.submitted | 2024-01-29 | - |
| dc.identifier.citation | 1. F. Mao, W. Ni, X. Xu, H. Wang, J. Wang, M. Ji, J. Li, Chemical Structure-Related Drug-Like Criteria of Global Approved Drugs. Molecules 2016, 21, 75.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/91692 | - |
| dc.description.abstract | 在藥物開發領域中，人們對於鄰位和間位取代的苯生物電子等排體的認識不斷增加，促進了其製備方法的發展。近年來提出幾種非共軛剛性碳氫化合物可作為苯生物電子等排體，其中發表較少的雙取代雙環[2.1.1]己烷具有相當高的潛力。因此我們提出了兩種可能的方法來獲得所需的5-取代雙環[2.1.1]己-1-醇和1-取代雙環[2.1.1]己-5-酮，分別是二碘化釤介導的環化和嚬哪醇重排反應。我們在二碘化釤介導的反應中得到不可預期的結果，而另一種重排方法已被證明可以成功建構雙環[2.1.1]己烷。該方法涉及連續的環丙烷化、嚬哪醇重排反應，將α-羥基矽基烯醇醚轉化為1-取代雙環[2.1.1]己-5-酮，此種雙環核心是製備鄰位取代苯生物電子等排體的關鍵中間體。為此，我們對雙環酮進行了多種官能基轉化，獲得多種1,5-雙取代的雙環[2.1.1]己烷衍生物。我們相信這些新方法可以有效解決合成鄰位取代苯生物電子等排體的障礙。 | zh_TW |
| dc.description.abstract | The increased recognition of ortho- and meta-substituted benzene bioisosteres in drug development has prompted the development of synthetic methods for their preparation. Several non-conjugated rigid hydrocarbons have been proposed as benzene bioisosteres, and among them, the less reported disubstituted bicyclo[2.1.1]hexanes (BCHs) have the potential to serve as bioisosteric frameworks. Herein, we propose two possible methods to obtain the desired 5-substituted bicyclo[2.1.1]hexan-1-ol and 1-substituted bicyclo[2.1.1]hexan-5-ones, namely SmI2-mediated cyclizations and pinacol rearrangement reactions. Despite encountering setbacks in the SmI2-mediated reaction, a simple and effective rearrangement approach was shown to deliver BCHs. This process involves the conversion of α-hydroxyl silyl enol ether to 1-substituted bicyclo[2.1.1]hexan-5-ones through a sequential cyclopropanation/pinacol rearrangement reaction. This bicyclic core was envisioned as a key intermediate for the preparation of ortho-substituted benzene bioisosteres. As such, several functional group interconversions were performed on the bicyclic ketone, resulting in various 1,5-disubstituted BCHs that could serve as ortho-substituted benzene bioisosteres. We believe these approaches offer a promising strategy to address the complex obstacles associated with the construction of bioisosteres resembling ortho-substituted benzenes. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-02-22T16:15:48Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-02-22T16:15:48Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | Content
口試委員審定書 i 誌謝 ii 摘要 iii Abstract iv Content v List of Abbreviations vii List of Figures x List of Schemes xi List of Tables xiii Chapter 1 Introduction 1 1.1 The Importance of Benzene Ring 1 1.2 Development of Bioisosteres and Benzene Bioisosteres 6 1.3 SmI2-mediated Cross-coupling Reaction 20 1.4 1,2-Rearrangment 23 Chapter 2 Experimental Design 28 Chapter 3 Result and Discussion 32 3.1 Synthesis of 5-substituted bicyclo[2.1.1]hexan-1-ol via SmI2-mediated cyclization 32 3.1.1 Synthesis of starting material 32 3.1.2 SmI2-mediated Barbier reaction 36 3.1.3 Ketyl-olefin type SmI2-mediated cyclization 38 3.1.4 Conclusion 39 3.2 Synthesis of 1-substituted Bicyclo[2.1.1]hexan-5-one and its Derivatives via Pinacol Rearrangement Reaction 40 3.2.1 Synthesis of 1-phenyl bicyclo[2.1.1]hexan-5-one 40 3.2.2 Functionalization of 1-phenyl bicyclo[2.1.1]hexan-5-one 43 3.2.3 Conclusion 52 Chapter 4 Experimental Section 55 4.1 General Information 55 4.2 Physical and Analytical Measurements 55 4.3 Synthetic Methods 56 Reference 81 Chapter 5. Supplementary Information 97 5.1 Crystallographic Data (X-Ray) of 109 97 5.2 checkCIF report of 109 104 5.3 NMR Spectrum 108 | - |
| dc.language.iso | en | - |
| dc.subject | 雙環[2.1.1]己烷 | zh_TW |
| dc.subject | 生物電子等排體 | zh_TW |
| dc.subject | 二碘化釤 | zh_TW |
| dc.subject | 酮 | zh_TW |
| dc.subject | 頻哪醇重排 | zh_TW |
| dc.subject | Bioisostere | en |
| dc.subject | Pinacol rearrangement | en |
| dc.subject | SmI2 | en |
| dc.subject | Ketone | en |
| dc.subject | Bicyclo[2.1.1]hexanes | en |
| dc.title | 利用二碘化釤介導的環化和頻哪醇重排合成雙環[2.1.1]己烷衍生物作為鄰位取代的苯生物電子等排體 | zh_TW |
| dc.title | Synthesis of Bicyclo[2.1.1]hexane Derivatives as ortho-Substituted Benzene Bioisosteres via SmI2-mediated Cyclization and Pinacol Rearrangement | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 方俊民;林文偉 | zh_TW |
| dc.contributor.oralexamcommittee | Jim-Min Fang;Wen-Wei Lin | en |
| dc.subject.keyword | 生物電子等排體,雙環[2.1.1]己烷,頻哪醇重排,酮,二碘化釤, | zh_TW |
| dc.subject.keyword | Bioisostere,Bicyclo[2.1.1]hexanes,Pinacol rearrangement,Ketone,SmI2, | en |
| dc.relation.page | 154 | - |
| dc.identifier.doi | 10.6342/NTU202400272 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2024-02-01 | - |
| dc.contributor.author-college | 理學院 | - |
| dc.contributor.author-dept | 化學系 | - |
| dc.date.embargo-lift | 2029-01-26 | - |
| 顯示於系所單位： | 化學系 | |
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|---|---|---|---|
| ntu-112-1.pdf 此日期後於網路公開 2029-01-26 | 6.12 MB | Adobe PDF |
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