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Synthesis of brain-targeted 1-(2-deoxy-2-fluoro-β- D-ribofuranosyl)-( E)-5-(2-iodovinyl)uracil coupled to a dihydropyridine ⇋ pyridinium salt redox chemical-delivery system
1-(2-Deoxy-2-fluoro-β- d-ribofuranosyl-( E)-5-(2-iodovinyl)uracil (IVFRU) was coupled to a dihydropyridine ⇋ pyridinium salt redox chemical-delivery system (CDS) via a cleavable sugar-ester linkage as a site-directed approach to increase diffusion of the parent nucleoside into the central nervous sy...
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| Published in: | Carbohydrate research 1993-10, Vol.249 (1), p.109-116 |
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| Language: | English |
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| container_end_page | 116 |
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| container_title | Carbohydrate research |
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| creator | Morin, Kevin W. Wiebe, Leonard I. Knaus, Edward E. |
| description | 1-(2-Deoxy-2-fluoro-β-
d-ribofuranosyl-(
E)-5-(2-iodovinyl)uracil (IVFRU) was coupled to a dihydropyridine ⇋ pyridinium salt redox chemical-delivery system (CDS) via a cleavable sugar-ester linkage as a site-directed approach to increase diffusion of the parent nucleoside into the central nervous system. Treatment of 1-(2-deoxy-2-fluoro-β-
d-ribofuranosyl)uracil with Bu
tMe
2SiCl in the presence of imidazole in DMF yielded the protected 5-
O-
tert-butyldimethylsilyl derivative. Subsequent reaction with nicotinoyl chloride hydrochloride in pyridine afforded 1-[5-
O-tert-butyldimethylsilyl-2-deoxy-2-fluoro-3-
O-(3-pyridylcarbonyl)-β-
d- ribofuranosyl]uracil. Reaction with iodine monochloride in methanol simultaneously cleaved the silyl ether moiety and iodinated the uracil ring at the 5-position. Coupling with (
E)-Bu
3Sn-CHCH-SiMe
3 in the presence of (Ph
3P)
2Pd
2(II)Cl
2 in THF gave 1-[2-deoxy-2-fluoro-3-
O- (3-pyridylcarbonyl)-β-
d-ribofuranosyl]-(
E)-5-(2-trimethylsilylvinyl)uracil. Quaternization with iodomethane in acetone yielded the
N-methylpyridinium iodide salt. Iodination of the reactive (
E)-trimethylsilylvinyl moiety with iodine monchloride in acetonitrile and reduction of the quaternary pyridinium iodide salt with sodium dithionite in the presence of sodium bydrogen carbonate was carried out as a one-pot procedure to afford 1-[2-deoxy-2-fluoro-3-
O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-β-
d- ribofuransyl]-(
E)-5-(2-iodovinyl)uracil (IVFRU-CDS). This synthetic strategy is readily amenable to the high specfi-activity radioiodination of IVFRU. |
| doi_str_mv | 10.1016/0008-6215(93)84064-D |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_76114130</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>000862159384064D</els_id><sourcerecordid>745650979</sourcerecordid><originalsourceid>FETCH-LOGICAL-c304t-fe15c7e9500f79d4978e24fe93681e005d770a271547be7cad49658d6aa7c2b03</originalsourceid><addsrcrecordid>eNp9kU2O1DAQhSMEGpqBG4DkFXQvDHbin2QzEpoefqSRWAASO8uxK7SREzd20pqcgAWHQeIgHIKT4NCtWc6qVPW-qifVK4qnlLykhIpXhJAai5LydVNtakYEw9t7xYrWssKsFF_uF6tb5GHxKKVvuSVCirPirC55yVmzKn59nIdxB8klFDrURu0GPOr4FUawiOJ1iS2EmxmXuPNTiAH_-Y3RFkfXhm6Keghp9hu8RlcbzBfaBRsObsjDrBrnkQnT3udbY0AaWbebbQz7OTrrBkB_f_xEp8ZNPUrajyiCDTfI7KB3Rvts790B4ozSnEboHxcPOu0TPDnV8-Lzm6tPl-_w9Ye37y9fX2NTETbiDig3EhpOSCcbyxpZQ8k6aCpRUyCEWymJLiXlTLYgjc6I4LUVWktTtqQ6L54f7-5j-D5BGlXvkgHv9QBhSkoKShmtFvDF3SDjgpNGNplkR9LEkFKETu2j63WcFSVqSVQtcaklLtVU6n-iapvXnp0MprYHe7t0ijDrF0cd8jsODqJKxsFgwLoIZlQ2uLsN_gEGYLKb</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>745650979</pqid></control><display><type>article</type><title>Synthesis of brain-targeted 1-(2-deoxy-2-fluoro-β- D-ribofuranosyl)-( E)-5-(2-iodovinyl)uracil coupled to a dihydropyridine ⇋ pyridinium salt redox chemical-delivery system</title><source>Backfile Package - Organic Chemistry (Legacy) [YCO]</source><creator>Morin, Kevin W. ; Wiebe, Leonard I. ; Knaus, Edward E.</creator><creatorcontrib>Morin, Kevin W. ; Wiebe, Leonard I. ; Knaus, Edward E.</creatorcontrib><description>1-(2-Deoxy-2-fluoro-β-
d-ribofuranosyl-(
E)-5-(2-iodovinyl)uracil (IVFRU) was coupled to a dihydropyridine ⇋ pyridinium salt redox chemical-delivery system (CDS) via a cleavable sugar-ester linkage as a site-directed approach to increase diffusion of the parent nucleoside into the central nervous system. Treatment of 1-(2-deoxy-2-fluoro-β-
d-ribofuranosyl)uracil with Bu
tMe
2SiCl in the presence of imidazole in DMF yielded the protected 5-
O-
tert-butyldimethylsilyl derivative. Subsequent reaction with nicotinoyl chloride hydrochloride in pyridine afforded 1-[5-
O-tert-butyldimethylsilyl-2-deoxy-2-fluoro-3-
O-(3-pyridylcarbonyl)-β-
d- ribofuranosyl]uracil. Reaction with iodine monochloride in methanol simultaneously cleaved the silyl ether moiety and iodinated the uracil ring at the 5-position. Coupling with (
E)-Bu
3Sn-CHCH-SiMe
3 in the presence of (Ph
3P)
2Pd
2(II)Cl
2 in THF gave 1-[2-deoxy-2-fluoro-3-
O- (3-pyridylcarbonyl)-β-
d-ribofuranosyl]-(
E)-5-(2-trimethylsilylvinyl)uracil. Quaternization with iodomethane in acetone yielded the
N-methylpyridinium iodide salt. Iodination of the reactive (
E)-trimethylsilylvinyl moiety with iodine monchloride in acetonitrile and reduction of the quaternary pyridinium iodide salt with sodium dithionite in the presence of sodium bydrogen carbonate was carried out as a one-pot procedure to afford 1-[2-deoxy-2-fluoro-3-
O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-β-
d- ribofuransyl]-(
E)-5-(2-iodovinyl)uracil (IVFRU-CDS). This synthetic strategy is readily amenable to the high specfi-activity radioiodination of IVFRU.</description><identifier>ISSN: 0008-6215</identifier><identifier>EISSN: 1873-426X</identifier><identifier>DOI: 10.1016/0008-6215(93)84064-D</identifier><identifier>PMID: 8252549</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Animals ; Antiviral Agents - chemical synthesis ; Antiviral Agents - chemistry ; Antiviral Agents - metabolism ; Biological Transport ; Brain - metabolism ; Floxuridine - analogs & derivatives ; Floxuridine - chemical synthesis ; Floxuridine - chemistry ; Floxuridine - metabolism ; Molecular Structure ; Oxidation-Reduction ; Pyridines - chemical synthesis ; Pyridines - chemistry ; Pyridines - metabolism</subject><ispartof>Carbohydrate research, 1993-10, Vol.249 (1), p.109-116</ispartof><rights>1993</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c304t-fe15c7e9500f79d4978e24fe93681e005d770a271547be7cad49658d6aa7c2b03</citedby><cites>FETCH-LOGICAL-c304t-fe15c7e9500f79d4978e24fe93681e005d770a271547be7cad49658d6aa7c2b03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/000862159384064D$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,786,790,3624,27957,27958,46044</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8252549$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Morin, Kevin W.</creatorcontrib><creatorcontrib>Wiebe, Leonard I.</creatorcontrib><creatorcontrib>Knaus, Edward E.</creatorcontrib><title>Synthesis of brain-targeted 1-(2-deoxy-2-fluoro-β- D-ribofuranosyl)-( E)-5-(2-iodovinyl)uracil coupled to a dihydropyridine ⇋ pyridinium salt redox chemical-delivery system</title><title>Carbohydrate research</title><addtitle>Carbohydr Res</addtitle><description>1-(2-Deoxy-2-fluoro-β-
d-ribofuranosyl-(
E)-5-(2-iodovinyl)uracil (IVFRU) was coupled to a dihydropyridine ⇋ pyridinium salt redox chemical-delivery system (CDS) via a cleavable sugar-ester linkage as a site-directed approach to increase diffusion of the parent nucleoside into the central nervous system. Treatment of 1-(2-deoxy-2-fluoro-β-
d-ribofuranosyl)uracil with Bu
tMe
2SiCl in the presence of imidazole in DMF yielded the protected 5-
O-
tert-butyldimethylsilyl derivative. Subsequent reaction with nicotinoyl chloride hydrochloride in pyridine afforded 1-[5-
O-tert-butyldimethylsilyl-2-deoxy-2-fluoro-3-
O-(3-pyridylcarbonyl)-β-
d- ribofuranosyl]uracil. Reaction with iodine monochloride in methanol simultaneously cleaved the silyl ether moiety and iodinated the uracil ring at the 5-position. Coupling with (
E)-Bu
3Sn-CHCH-SiMe
3 in the presence of (Ph
3P)
2Pd
2(II)Cl
2 in THF gave 1-[2-deoxy-2-fluoro-3-
O- (3-pyridylcarbonyl)-β-
d-ribofuranosyl]-(
E)-5-(2-trimethylsilylvinyl)uracil. Quaternization with iodomethane in acetone yielded the
N-methylpyridinium iodide salt. Iodination of the reactive (
E)-trimethylsilylvinyl moiety with iodine monchloride in acetonitrile and reduction of the quaternary pyridinium iodide salt with sodium dithionite in the presence of sodium bydrogen carbonate was carried out as a one-pot procedure to afford 1-[2-deoxy-2-fluoro-3-
O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-β-
d- ribofuransyl]-(
E)-5-(2-iodovinyl)uracil (IVFRU-CDS). This synthetic strategy is readily amenable to the high specfi-activity radioiodination of IVFRU.</description><subject>Animals</subject><subject>Antiviral Agents - chemical synthesis</subject><subject>Antiviral Agents - chemistry</subject><subject>Antiviral Agents - metabolism</subject><subject>Biological Transport</subject><subject>Brain - metabolism</subject><subject>Floxuridine - analogs & derivatives</subject><subject>Floxuridine - chemical synthesis</subject><subject>Floxuridine - chemistry</subject><subject>Floxuridine - metabolism</subject><subject>Molecular Structure</subject><subject>Oxidation-Reduction</subject><subject>Pyridines - chemical synthesis</subject><subject>Pyridines - chemistry</subject><subject>Pyridines - metabolism</subject><issn>0008-6215</issn><issn>1873-426X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><recordid>eNp9kU2O1DAQhSMEGpqBG4DkFXQvDHbin2QzEpoefqSRWAASO8uxK7SREzd20pqcgAWHQeIgHIKT4NCtWc6qVPW-qifVK4qnlLykhIpXhJAai5LydVNtakYEw9t7xYrWssKsFF_uF6tb5GHxKKVvuSVCirPirC55yVmzKn59nIdxB8klFDrURu0GPOr4FUawiOJ1iS2EmxmXuPNTiAH_-Y3RFkfXhm6Keghp9hu8RlcbzBfaBRsObsjDrBrnkQnT3udbY0AaWbebbQz7OTrrBkB_f_xEp8ZNPUrajyiCDTfI7KB3Rvts790B4ozSnEboHxcPOu0TPDnV8-Lzm6tPl-_w9Ye37y9fX2NTETbiDig3EhpOSCcbyxpZQ8k6aCpRUyCEWymJLiXlTLYgjc6I4LUVWktTtqQ6L54f7-5j-D5BGlXvkgHv9QBhSkoKShmtFvDF3SDjgpNGNplkR9LEkFKETu2j63WcFSVqSVQtcaklLtVU6n-iapvXnp0MprYHe7t0ijDrF0cd8jsODqJKxsFgwLoIZlQ2uLsN_gEGYLKb</recordid><startdate>19931018</startdate><enddate>19931018</enddate><creator>Morin, Kevin W.</creator><creator>Wiebe, Leonard I.</creator><creator>Knaus, Edward E.</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>19931018</creationdate><title>Synthesis of brain-targeted 1-(2-deoxy-2-fluoro-β- D-ribofuranosyl)-( E)-5-(2-iodovinyl)uracil coupled to a dihydropyridine ⇋ pyridinium salt redox chemical-delivery system</title><author>Morin, Kevin W. ; Wiebe, Leonard I. ; Knaus, Edward E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c304t-fe15c7e9500f79d4978e24fe93681e005d770a271547be7cad49658d6aa7c2b03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Animals</topic><topic>Antiviral Agents - chemical synthesis</topic><topic>Antiviral Agents - chemistry</topic><topic>Antiviral Agents - metabolism</topic><topic>Biological Transport</topic><topic>Brain - metabolism</topic><topic>Floxuridine - analogs & derivatives</topic><topic>Floxuridine - chemical synthesis</topic><topic>Floxuridine - chemistry</topic><topic>Floxuridine - metabolism</topic><topic>Molecular Structure</topic><topic>Oxidation-Reduction</topic><topic>Pyridines - chemical synthesis</topic><topic>Pyridines - chemistry</topic><topic>Pyridines - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Morin, Kevin W.</creatorcontrib><creatorcontrib>Wiebe, Leonard I.</creatorcontrib><creatorcontrib>Knaus, Edward E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Carbohydrate research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Morin, Kevin W.</au><au>Wiebe, Leonard I.</au><au>Knaus, Edward E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis of brain-targeted 1-(2-deoxy-2-fluoro-β- D-ribofuranosyl)-( E)-5-(2-iodovinyl)uracil coupled to a dihydropyridine ⇋ pyridinium salt redox chemical-delivery system</atitle><jtitle>Carbohydrate research</jtitle><addtitle>Carbohydr Res</addtitle><date>1993-10-18</date><risdate>1993</risdate><volume>249</volume><issue>1</issue><spage>109</spage><epage>116</epage><pages>109-116</pages><issn>0008-6215</issn><eissn>1873-426X</eissn><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-1</notes><notes>content type line 23</notes><notes>ObjectType-Article-1</notes><notes>ObjectType-Feature-2</notes><abstract>1-(2-Deoxy-2-fluoro-β-
d-ribofuranosyl-(
E)-5-(2-iodovinyl)uracil (IVFRU) was coupled to a dihydropyridine ⇋ pyridinium salt redox chemical-delivery system (CDS) via a cleavable sugar-ester linkage as a site-directed approach to increase diffusion of the parent nucleoside into the central nervous system. Treatment of 1-(2-deoxy-2-fluoro-β-
d-ribofuranosyl)uracil with Bu
tMe
2SiCl in the presence of imidazole in DMF yielded the protected 5-
O-
tert-butyldimethylsilyl derivative. Subsequent reaction with nicotinoyl chloride hydrochloride in pyridine afforded 1-[5-
O-tert-butyldimethylsilyl-2-deoxy-2-fluoro-3-
O-(3-pyridylcarbonyl)-β-
d- ribofuranosyl]uracil. Reaction with iodine monochloride in methanol simultaneously cleaved the silyl ether moiety and iodinated the uracil ring at the 5-position. Coupling with (
E)-Bu
3Sn-CHCH-SiMe
3 in the presence of (Ph
3P)
2Pd
2(II)Cl
2 in THF gave 1-[2-deoxy-2-fluoro-3-
O- (3-pyridylcarbonyl)-β-
d-ribofuranosyl]-(
E)-5-(2-trimethylsilylvinyl)uracil. Quaternization with iodomethane in acetone yielded the
N-methylpyridinium iodide salt. Iodination of the reactive (
E)-trimethylsilylvinyl moiety with iodine monchloride in acetonitrile and reduction of the quaternary pyridinium iodide salt with sodium dithionite in the presence of sodium bydrogen carbonate was carried out as a one-pot procedure to afford 1-[2-deoxy-2-fluoro-3-
O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-β-
d- ribofuransyl]-(
E)-5-(2-iodovinyl)uracil (IVFRU-CDS). This synthetic strategy is readily amenable to the high specfi-activity radioiodination of IVFRU.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>8252549</pmid><doi>10.1016/0008-6215(93)84064-D</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0008-6215 |
| ispartof | Carbohydrate research, 1993-10, Vol.249 (1), p.109-116 |
| issn | 0008-6215 1873-426X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_76114130 |
| source | Backfile Package - Organic Chemistry (Legacy) [YCO] |
| subjects | Animals Antiviral Agents - chemical synthesis Antiviral Agents - chemistry Antiviral Agents - metabolism Biological Transport Brain - metabolism Floxuridine - analogs & derivatives Floxuridine - chemical synthesis Floxuridine - chemistry Floxuridine - metabolism Molecular Structure Oxidation-Reduction Pyridines - chemical synthesis Pyridines - chemistry Pyridines - metabolism |
| title | Synthesis of brain-targeted 1-(2-deoxy-2-fluoro-β- D-ribofuranosyl)-( E)-5-(2-iodovinyl)uracil coupled to a dihydropyridine ⇋ pyridinium salt redox chemical-delivery system |
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