Catalytic asymmetric synthesis of carbocyclic C-nucleosides

Sourabh Mishra; Florian C T Modicom; Conor L Dean; Stephen P Fletcher

doi:10.1038/s42004-022-00773-6

Catalytic asymmetric synthesis of carbocyclic C-nucleosides

Commun Chem. 2022;5(1):154. doi: 10.1038/s42004-022-00773-6. Epub 2022 Nov 19.

Authors

Sourabh Mishra¹, Florian C T Modicom¹, Conor L Dean¹, Stephen P Fletcher¹

Affiliation

¹ Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA UK.

Abstract

Access to carbocyclic C-nucleosides (CC-Ns) is currently restricted. The few methods available to make CC-Ns suffer from long syntheses and poor modularity, hindering the examination of potentially important chemical space. Here we report an approach to CC-Ns which uses an asymmetric Suzuki-Miyaura type reaction as the key C-C bond forming step. After coupling the densely functionalized racemic bicyclic allyl chloride and heterocyclic boronic acids, the trisubstituted cyclopentenyl core is elaborated to RNA analogues via a hydroborylation-homologation-oxidation sequence. We demonstrate that the approach can be used to produce a variety of enantiomerically enriched CC-Ns, including a carbocyclic derivative of Showdomycin.

Keywords: Asymmetric catalysis; Asymmetric synthesis; Synthetic chemistry methodology.