Synthesis of methylenecyclobutane analogues of nucleosides with axial chirality and their phosphoralaninates: a new pronucleotide effective against Epstein-Barr virus.

Methylenecyclobutane analogues of 2'-deoxyadenosine, 2'-deoxyguanosine and 2'-deoxycytidine, and the corresponding phosphoralaninate pronucleotides comprising adenine and guanine bases, were synthesized as potential antiviral agents. Phosphoralaninate of adenine methylenecyclobutane was a potent inhibitor of replication of Epstein-Barr virus (EBV) in Daudi cell culture. Phosphoralaninate of guanine analogue was inactive but both pronucleotides were substrates for porcine liver esterase. Adenine methylenecyclobutane analogue was deaminated by adenosine deaminase.