The cyclohexene ring system as a furanose mimic: Synthesis and antiviral activity of both enantiomers of cyclohexenylguanine

Both enantiomers of cyclohexenylguanine were synthesized in a stereospecifi c way starting from the same starting material: R-(-)-carvone. Both compoun ds showed potent-and selective anti-herpesvirus activity (HSV-1, HSV-2, VZV , CMV). The binding of both cyclohexene nucleosides in the active site of H SV-1 thymidine kinase was investigated, and a model for the binding of both enantiomers is proposed. The amino acids involved in binding of the optica l antipodes are the same, but the interaction energy of both enantiomers is slightly different. This may be attributed to the interaction of the secon dary hydroxyl function of the nucleoside analogues with Glu-225. Structural analysis has demonstrated the flexibility of the cyclohexenyl system, and this may be considered as an important conformational characteristic explai ning the potent antiviral activity.