Synthesis of Enantiomerically Pure 1′,2′-cis-dideoxy, -dideoxydi­dehydro, -ribo and -deoxy Carbocyclic Nucleoside Analogues

We describe a short and stereospecific synthesis of different series of 1′,2′-cis-disubstituted carbocyclic nucleoside analogues. All-natural nucleobases or their precursors are coupled in a microwave-assisted Mitsunobu-type reaction with enantiomerically pure (1R,2S)-2-(benzyloxymethyl)cyclopent-3-enol. By modifying the cyclopentene scaffold, our synthetic strategy gives access to a series of 1′,2′-cis-disubstituted carbocyclic nucleoside analogues of the dideoxy (dd), di­deoxydidehydro (d4) or the ribo series. The ribo series is synthesized in a more convenient way compared to a previous route. The deoxy series of 1′,2′-cis-disubstituted carbocyclic nucleoside analogues is prepared following an earlier reported approach. This synthesis involves the microwave-assisted coupling of (1R,2S,3S)-3-(benzyloxy)-2-[(benzyl­oxy)methyl]cyclopentan-1-ol with the appropriate nucleobases.

The first intermolecular interrupted imino-Nazarov reaction: expeditious access to carbocyclic nucleoside analogues

The first intermolecular interrupted imino-Nazarov reaction with silylated pyrimidine derivatives as nucleophile has been developed, furnishing carbocyclic nucleoside analogues in a one-pot operation.

A straightforward entry to chiral carbocyclic nucleoside analogues via the enantioselective [3+2] cycloaddition of α-nucleobase substituted acrylates

A straightforward entry to chiral carbocyclic nucleoside analogues is achievedviathe enantioselective [3+2] cycloaddition of α-nucleobase substituted acrylates to vinyl cyclopropanes.