1,3-Dioxan-5-yl pyrimidine nucleoside analogues, higher homologues of antiviral and anticancer
1,3-dioxolanes, were prepared from bis-1,3-tritylglycerol and 3-benzoylated bases (uracil, 5-fluorouracil, thymine). Mitsunobu condensation, deprotection, and cycloacetalization gave cis/trans
mixtures of 2,5-disubstituted-1,3-dioxanes in which the desired cis stereoisomers predominated.
Cytosine derivatives could not be obtained in this manner; N
4-benzoylcytosine afforded an O-2
alkylated Mitsunobu product that rearranged to an O
2-(2,3-dihydroxypropyl)cytosine on detritylation
with aqueous acetic acid. Cytosine and 5-fluorocytosine nucleosides were therefore prepared from
the corresponding uracils via their 1,2,4-triazole derivatives. 1H NMR data established the
conformational preference for equatorial 2‘-hydroxymethyl and axial 5‘-base in the cis isomers;
the trans compounds were diequatorial. Despite their conformations, the cis nucleosides showed
no antiviral activity.
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