Syntheses of 1,3-dioxolanyl and carbocyclic nucleosides as potential antiviral agnets [sic]
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The focus of this thesis is on the asymmetric synthesis of dioxolane and various novel carbocyclic nucleoside analogues with antiviral activity. Enantiomerically pure 5-alkyluracil-1,3-dioxolane nucleoside analogues were synthesized by palladium mediated cross-Stille coupling reaction from L-gulono-?-lactone in 17 steps. The synthetic methodology of enantiomerically pure key intermediates for carbocyclic nucleosides, D- and L-2-cyclopentenone, were developed by ring-closing metathesis reaction from D-ribose in 8 steps, which were utilized to synthesize D-cyclopetenyl and cyclopentyl nucleosides. Among them, D-cyclopetenyl adenine, cytosine and 5-F-cytosine analogues were found to be active against orthopox virus including smallpox, monkeypox, and cowpox virus. Enantiomerically pure D-2’-fluoro-2’,3’-dideoxy-2’,3’-didehydro and D-3’-fluoro-2’,3’- dideoxy-2’,3’-didehydro carbocyclic nucleosides were synthesized using epoxide ring opening reduction from D-ribose in 24 and 23 steps, respectively.