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Synthesis of Homoaristeromycin Analogues as Potent antiviral agents

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dc.contributor.advisor정낙신-
dc.contributor.author신영섭-
dc.date.accessioned2018-05-29T04:44:01Z-
dc.date.available2021-04-13T04:16:51Z-
dc.date.issued2018-02-
dc.identifier.other000000150495-
dc.identifier.urihttps://hdl.handle.net/10371/142237-
dc.description학위논문 (석사)-- 서울대학교 대학원 : 약학대학 약학과, 2018. 2. 정낙신.-
dc.description.abstract(-)-Aristeromycin (1) exhibits significant antiviral activity through inhibition of S-adenosylhomocysteine (SAH) hydrolase, which has been a promising target for many broad antiviral agents. However, its therapeutic utility has been limited due to its the significant toxicity. This cytotoxicity arise from 5'-phosphorylation to the corresponding nucleotides by cellular kinase. To lower cytotoxicity, an approach of extending the C-5' hydroxymethyl side chain by one carbon homologation was made to provide the C-5' homolog of (-)-aristeromycin. Furthermore, we thought that introduction of fluorine atom at 6'-position which is bioisostere with hydrogen atom improves antiviral activity by SAH hydrolase inhibitory effect.
Based on these strategy, 6'-fluoro-homoaristeromycin analogues were designed and synthesized via Michael reaction and stereoselective electrophilic fluorination as key steps. (‒)-6'-b-Fluoro-homoaristeromycin (3) showed potent inhibition of SAH hydrolase (IC50 = 0.36 nM), high anti-Chikungunya activity (EC50 = 0.12 uM) and low cytotoxicity (CC50 > 250 uM). Selectivity index is more than 2087.
In brief, the (‒)-6'-b-fluoro-homoaristeromycin (3) showed potent activity against Chikungunya virus and low toxicity. This study can be extensively applied to the development of potent antiviral agents.
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dc.description.tableofcontentsI. Introduction 1

II. Results and Discussion 4

III. Conclusion 13

IV. Experimental Section 13

V. References 35

VI. 1H and 13C NMR Copies 36

VII. 국문초록 58
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dc.formatapplication/pdf-
dc.format.extent3411835 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subjectAntiviral-
dc.subjectAristeromycin-
dc.subjectCarbocyclic nucleoside-
dc.subjectFluorination-
dc.subjectChikungunya virus-
dc.subject.ddc615-
dc.titleSynthesis of Homoaristeromycin Analogues as Potent antiviral agents-
dc.typeThesis-
dc.description.degreeMaster-
dc.contributor.affiliation약학대학 약학과-
dc.date.awarded2018-02-
Appears in Collections:
College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Theses (Master's Degree_약학과)
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