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dc.contributor.advisor최선-
dc.contributor.author류승연-
dc.creator류승연-
dc.date.accessioned2017-08-28T08:02:37Z-
dc.date.available2017-08-28T08:02:37Z-
dc.date.issued2014-
dc.identifier.urihttp://dspace.ewha.ac.kr/handle/2015.oak/210864-
dc.identifier.urihttp://dcollection.ewha.ac.kr/jsp/common/DcLoOrgPer.jsp?sItemId=000000084933-
dc.description.abstractOn 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.tableofcontentsⅠ. 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.formatapplication/pdf-
dc.format.extent678477 bytes-
dc.languageeng-
dc.publisher이화여자대학교 대학원-
dc.subject.ddc600-
dc.titleSynthesis of Truncated C8-Modified-4'-thionucleosides as Potential HSP90 Inhibitors-
dc.typeMaster's Thesis-
dc.format.pagev, 55 p.-
dc.identifier.thesisdegreeMaster-
dc.identifier.major대학원 약학과-
dc.date.awarded2014. 2-
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일반대학원 > 약학과 > Theses_Master
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