Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 권성희 | - |
dc.creator | 권성희 | - |
dc.date.accessioned | 2016-08-25T06:08:05Z | - |
dc.date.available | 2016-08-25T06:08:05Z | - |
dc.date.issued | 2002 | - |
dc.identifier.other | OAK-000000029820 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/181959 | - |
dc.identifier.uri | http://dcollection.ewha.ac.kr/jsp/common/DcLoOrgPer.jsp?sItemId=000000029820 | - |
dc.description.abstract | Apio dideoxynucleosides (apio ddNs) which belong to novel class of nucleosides in that oxygen of the furanose and C2'-methylene are transposed, were reported to show anti-HIV activity and better profile about enzymatic deamination and glycosyl bond hydrolysis than 2',3'-dideoxynucleosides (ddNs). On the other hand, many L-nucleosides were found to be less cytotoxic than the corresponding D-nucleosides while maintaining their antiviral activities or sometimes possessing better antiviral activities. On the basis of these findings, we synthesized D- and L-apio cytidine derivatives were synthesized to compare their antiviral activity with that of parent nucleosides. Novel n- and L-2'-hydroxy substituted apio cytidines have been synthesized, starting from D-galactose via exocyclic methylene sugar 4 as a key intermediate. Stereocontrol (S-configuration) of the C3'position for D-nucleosides was accomplished using stereoselective dihydroxylation of 4 followed by stereoselective deoxygenation. Stereocontrol (R-cofiguration) of the C3'position for L-nucleosides was achieved using stereoselective hydroboration of 4 with bulky 9-BBN followed by oxidation with sodium perborate. The glycosyl donors, 2 and 6 were condensed with N^(4)-benzoylcytosine in the presence of TMSOTf to give the protected nucleosides, respectively. Deprotection of D- and L-anomers afforded D-apio analogue 1 and L-apio analogues 5a and 5b, respectively. The final nucleosides 1,5a and 5b were tested against HIV-1 in MT-4 cells. They were found to be neither active nor cytotoxic up to 100μM.;Apio dideoxynucleosides는 furanose ring의 산소와 C2'의 methylene기의 위치가 바꿔 새로운 계열의 nucleosides에 속하는 물질로서 항 HIV활성이 있으며 기존의 dideoxynucleosides 보다 바이러스 효소에 의한 deamination 및 glycosyl bond의 가수분해 작용이 적은 것으로 알려져있다. 최근에는 천연의 D-nucleosides 보다 독성이 적은 L-nucleosides가 보다 뛰어난 항바이러스 효과를 가지고 있음이 보고되고 있기 때문에 D체 뿐만 아니라 L체의 apio cytidine 유도체들을 합성하였다. D-galactose로부터 D체와 L체의 공통 중간체인 olefine 4를 합성하고 1,2-acetonide의 steric effect를 이용하여 C3에서 수산화 메틸기의 위치 선택성을 결정하였다. D-nucleoside를 유도하기 위해서 4로부터 dihydroxylation과 deoxygenation을 거쳐서 12 (s-configuration)를 합성하였고 L-nucleosides를 얻기 위해 4로 부터 hydroration과 산화과정을 거쳐서 7(R-configuration)을 합성하였다. 이들을 Ν^(4)-benzoylcytosine과 축합하여 D체인 1과 L체인 5a 및 5b를 얻을 수 있었다. 이들은 MT-4 세포에서 100 μM까지 항 HIV-1 효과가 없는 것으로 나타났으며 다른 항바이러스 활성을 측정중에 있다. | - |
dc.description.tableofcontents | Abstract = ⅲ Ⅰ. Introduction = 1 Ⅱ. Results and discussion = 8 Ⅲ. Conclusion = 21 Ⅳ. Experimental section = 22 Ⅴ. References = 42 국문초록 = 45 감사의 글 = 46 | - |
dc.format | application/pdf | - |
dc.format.extent | 1499628 bytes | - |
dc.language | eng | - |
dc.publisher | The Graduate School of Ewha Womans University | - |
dc.subject | Asymmetric Synthesis | - |
dc.subject | Anti-HIV-I | - |
dc.subject | Hydroxy-Substituted Apio | - |
dc.subject | Dideoxynucleosides | - |
dc.title | Asymmetric Synthesis and Anti-HIV-I Activity of Hydroxy-Substituted Apio Dideoxynucleosides | - |
dc.type | Master's Thesis | - |
dc.format.page | 47 p. : ill. | - |
dc.identifier.thesisdegree | Master | - |
dc.identifier.major | 대학원 약학과 | - |
dc.date.awarded | 2003. 2 | - |