Synthesis of Janus type nucleoside analogues and their preliminary bioactivity.

Novel Janus type nucleoside analogues 1a and 1b were synthesized in seven steps from 2-amino-4,6-dihydroxypyrimidine and 4,6-dihydroxypyrimidine. The base moiety of 1a has one face with a Watson-Crick donor-donor-acceptor (DDA) H-bond array of guanine and the other face with an acceptor-acceptor-donor (AAD) array of cytosine, which might lead to its base pairing with either cytosine or guanine due to the rotating of the glycosyl bond. This property may enable Janus type nucleoside analogues to act as an antiviral compound in a similar way to ribavirin. Both 1a and 1b were screened by a vitro HBV DNA replication inhibition test and indeed 1a showed a great potential with IC(50) = 10 µM and SI = 78.9 for antiviral drug development.