Synthesis, Conformational Analysis, and Biological Activity of a Rigid Carbocyclic Analogue of 2′-Deoxy Aristeromycin Built on a Bicyclo[3.1.0]hexane Template

Abstract
A new chiral synthesis of the pseudosugar synthon (1R,2S,4R,5S)-1-[(benzyloxy)methyl]-2-tert-butyloxy-4-hydroxybicyclo[3.1.0]hexane (12) is reported. This compound was used as a template for the construction of carbocyclic nucleoside 4, a conformationally rigid analogue of 2′-deoxyaristeromycin. The X-ray structure and 1H NMR analysis confirmed the exclusive North [2′-exo (2E)] conformation of 4 which is vastly different from that of other non-rigid carbocyclic nucleosides. Compound 4 showed good in vitro antiviral activity against human cytomegalovirus and EBV with minimal cytotoxicity.