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Synthesis of 3′-Amino-2′,3′-dideoxy-hexofuranose Nucleosides with Potential Anti-Viral Activity

✍ Scribed by Jesper Lau; Erik B. Pedersen; Lars V. Jensen; Carsten M. Nielsen


Publisher
John Wiley and Sons
Year
1991
Tongue
English
Weight
682 KB
Volume
324
Category
Article
ISSN
0365-6233

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✦ Synopsis


Michuel type addition of DBU (1,8diazabicyclo[5,4,O]undec-7ene) phthalimide salt to 4,6di-0-acetyl-2,3-dideoxy-uf&h~-D-ery1hro-Ir~-hex-2enme 2 and concomitant acetyl shift give an anomeric mixture of ambino and rib0 isomers of 5,6-di-0-acetyl-2,3~deo~y-3-ph~limjdo-D-hex~ furanose 3 which after acetylation at the anomeric hydroxy group is separated to give 4 and 5. Subsequent reaction with 5'-substituted silylated uracil in the presence of TMS-triflate results in three different 5',6'di-O-acetyl-2',3'dideoxy-3'-phthalimido-D-hexofuranose nucleosides 7,9, and 10 which were deprotected to give the corresponding 3'-amino nucleosides 8, ll, and 12. The compounds 7-12 were investigated for their activity against HSV-I and HIV-1. Synthese von 3'-Amino-2'~'~id~x~-hexoluranaPe-Nucl~ld~ mit potentieller antivlraler Aktivitiit Michael-artige-Addition von DBU (1.8-Diatabicyclo[5.4.0]undec-7-ene) phthalimidsalz an 4,6-Di-0-acetyl-2.3-didesoxy-u~~ehy~~D-e~~f~~~~hex-2-enose 2 und begleitende Acetylverschiebung ergaben eine anomere Mischung von urnhino-und ribo-Isomeren der 5,6-Di-0-~etyl-2,3-didesoxy-3-phthalimido-D-hexofumm 3. die nach Acetylierung der anomerischen Hydroxygruppe getrennt wurde und 4 und 5 lieferte. Nachfolgende Reaktion mit 5'-substituiertem silyliertem Urazil in Gegenwart von TMS-Triflate fiihrte zu drei versfhiedeaen 5',6'-Di-0-acetyl-2',3'didesoxy-3'phthalimido-Dhexofuranose-Nucleosiden 7,9 und 10. die deblockiert wurden und die korrespdierenden 3'-Amino-Nucleoside 8 , l l und 12 bildeten. Die Verbindungen 7-12 wurden auf ihre AktivitL gegen HSV-I und HIV-I untersucht.


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