Synthesis and antiviral activities of novel 2 ',4 '- or 3 ',4 '-doubly branched carbocyclic nucleosides as potential antiviral agents

Abstract

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(O) catalyst. Although all the synthesized compounds were assayed against several viruses, only the cytosine analogue 20 showed moderate antiviral activity against the human cytomegalovirus.