Synthesis and Antiviral Activities of Novel 2′, 4′‐ or 3′, 4′‐Doubly Branched Carbocyclic Nucleosides as Potential Antiviral Agents

In this study, a series of 2′, 4‐′ or 3′, 4′‐doubly branched carbocyclic nucleosides ( 11 , 12 , 19 , and 20 ) were synthesized from simple acyclic ketone derivatives as starting materials. The installation of the 4′‐quaternary carbon needed was carried out using a [3, 3]‐sigmatropic rearrangement. In addition, the introduction of a methyl group in the 2′‐ or 3′‐position was accomplished by either Grignard reaction or Horner‐Wadsworth‐Emmons reaction with triethyl‐2‐phosphonopropionate, respectively. Bis‐vinyl was successfully cyclized using a Grubbs' catalyst II. The natural bases (adenine, cytosine) were coupled efficiently using a Pd(0) catalyst. Although all the synthesized compounds were assayed against several viruses, only the cytosine analogue 20 showed moderate antiviral activity against the human cytomegalovirus.