Synthesis of Enantiomerically Pure 1 ',2 '-cis-dideoxy, -dideoxydi-dehydro, -ribo and -deoxy Carbocyclic Nucleoside Analogues

摘要

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 theribo 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.