Full metadata record
DC Field | Value | Language |
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dc.contributor.advisor | 최선 | - |
dc.contributor.author | 류승연 | - |
dc.creator | 류승연 | - |
dc.date.accessioned | 2016-08-26T04:08:02Z | - |
dc.date.available | 2016-08-26T04:08:02Z | - |
dc.date.issued | 2014 | - |
dc.identifier.other | OAK-000000084933 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/210864 | - |
dc.identifier.uri | http://dcollection.ewha.ac.kr/jsp/common/DcLoOrgPer.jsp?sItemId=000000084933 | - |
dc.description.abstract | On the basis of potent anticancer activity of Geldenamycin and PU3 (the first fully synthetic inhibitor of HSP90), the first series of truncated N6-substituted-C8-modified-4'-thioadenosine derivatives were designed and synthesized. The synthesis of truncated TBS protected glycosyl donor 10 was obtained starting from D-mannose. The large scale synthesis of 6-chloro-8-iodopurine was achieved by a sequence of lithiation, iodination, and the acid catalyzed deprotection. Modifications at the C8-position of 6-chloropurine derivatives were achieved using palladium-catalyzed cross coupling reactions (furanyl and thiophenyl) as key steps. A series of C8-substituted alkyl and benzylic amines were synthesized by aromatic nucleophilic substitution reactions. The synthesized C8 modified and N6-substituted 4'-thioadenosine derivatives, 17a, 17b, 19a, 19b, 21, and 24a-d are in biological assay as HSP90 inhibitors. ;Geldenamycin과 PU3 (최초로 합성된 HSP90 inhibitor)의 강한 항암효과에 근거하여, 최초의 truncated N6-substituted-C8-modified 4'-thio-adenosine 유도체들을 설계하고 합성하였다. D-Mannose로부터 TBS기로 protection된 truncated thio-glycosyl donor 10를 합성했고 lithiation과 Iodination reaction을 차례로 거쳐6-chloro-8-iodopurine의 대량합성 또한 성공하였다. 최종적으로, 산 촉매 조건 하의 THP치환기 제거반응으로 목표했던 6-chloro-8-iodopurine을 좋은 수율로 얻었다. 6-chloropurine의 C8 위치의 furanyl 혹은 thiophenyl 로의 변형은 Palladium 촉매의 cross coupling 을 주요반응으로 하여 일어나고, C8 위치의 alkyl기 혹은 benzylic amine 기로의 치환은 방향족 친핵성 치환반응으로 이루어졌다. 이렇게 합성된 C8-modified and N6-substituted 4'-thioadenosine 유도체들의 HSP90 억제제로서의 활성에 관한 생물학적 test가 진행 중에 있다. | - |
dc.description.tableofcontents | Ⅰ. Introduction 1 Ⅱ. Results and Discussion 11 A. Synthesis of the TBS protected glycosyl donor 10 12 B. Synthesis of the 6-chloro-8-iodopurine 14 14 C. Synthesis of Truncated C8-substituted 4'-thioadenosine Derivatives 15 16 D. Biological Activity Studies 22 Ⅲ. Conclusion 23 Ⅳ. Experimental Section 24 Ⅴ. References 51 Abstract in Korean 54 Acknowledgements 55 | - |
dc.format | application/pdf | - |
dc.format.extent | 678477 bytes | - |
dc.language | eng | - |
dc.publisher | 이화여자대학교 대학원 | - |
dc.subject.ddc | 600 | - |
dc.title | Synthesis of Truncated C8-Modified-4'-thionucleosides as Potential HSP90 Inhibitors | - |
dc.type | Master's Thesis | - |
dc.format.page | v, 55 p. | - |
dc.identifier.thesisdegree | Master | - |
dc.identifier.major | 대학원 약학과 | - |
dc.date.awarded | 2014. 2 | - |