Conformationally Locked Carbocyclic Nucleosides Built on a 4′- Hydroxymethyl-3′-hydroxybicyclo[4.1.0]heptane Template. Stereoselective Synthesis and Antiviral Activity

Two new families of enantiomerically pure carbocyclic nucleoside analogues based on a cyclohexane moiety with five chiral centers and a fused cyclopropyl ring have been synthesized. A highly regio-and stereoselective synthetic approach for the modular construction of the functionalized bicyclo[4.1.0]-heptyl azide intermediate 6 has been established. Key steps to achieve this asymmetric synthesis involved highly diastereoselec-tive allylic oxidation and hydroboration reactions. The first family of compounds, 1a,b and 2, presents different natural nucleobases, whereas the second one 3a-e bears functionalized 1,2,3-triazoles. These derivatives have been tested as antiviral agents, and compound 3d has shown to display moderate activity against coxsackie B4 virus.

Automated summary

A synthetic approach for the enantioselective synthesis of carbocyclic nucleoside analogues has been established, resulting in the synthesis of two new families of compounds. These compounds have been tested as antiviral agents and have shown moderate activity against coxsackie B4 virus.