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

Simon Weising; Patrick Dekiert; Dominique Schols; Johan Neyts; Chris Meier

doi:10.1055/s-0037-1609493

Synthesis, Table of Contents

Synthesis 2018; 50(11): 2266-2280
DOI: 10.1055/s-0037-1609493

paper

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

Simon Weising

^aOrganische Chemie, Fakultät für Mathematik, Informatik und Naturwissenschaften, Universität Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany Email: chris.meier@chemie.uni-hamburg.de

,

Patrick Dekiert

^aOrganische Chemie, Fakultät für Mathematik, Informatik und Naturwissenschaften, Universität Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany Email: chris.meier@chemie.uni-hamburg.de

,

Dominique Schols

^bKatholieke Universiteit Leuven, Rega Institute for Medical Research, Herestraat 49, 3000 Leuven, Belgium

,

Johan Neyts

^bKatholieke Universiteit Leuven, Rega Institute for Medical Research, Herestraat 49, 3000 Leuven, Belgium

,

Chris Meier*

^aOrganische Chemie, Fakultät für Mathematik, Informatik und Naturwissenschaften, Universität Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany Email: chris.meier@chemie.uni-hamburg.de

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Abstract

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Abstract

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.

Key words

carbocycles - Mitsunobu coupling - 1′,2′-cis-substitution - microwave reaction - nucleosides

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References

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Supporting Information

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

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