Synthesis of Janus type nucleoside analogues and their preliminary bioactivity

摘要

Novel Janus type nucleoside analogues la and lb were synthesized in seven steps from 2-amino-4,6-dihydroxypyrimidine and 4,6-dihydroxypyrimidine. The base moiety of la 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 la and lb were screened by a vitro HBV DNA replication inhibition test and indeed la showed a great potential with IC_50 = 10 μM and SI = 78.9 for antiviral drug development.