Synthesis and activity against HBV of novel tetra-seconucleoside analogues of dyphlline having the acyclic chains of ACV and HBG

Selective alkylation of dyphylline (1) with (2-aceloxyethoxy)methyl bromide (2a) or 4-acetoxybutyl bromide (2b) afforded 3'-O-[(acetoxyethoxy)methyl]dyphylline (3a) and 3'-O-(4-acetoxybutyl)dyphylline (3b), respectively. A trans esterification process rather than alkylation of the dihydroxypropyl side chain in I had taken place during the reaction with 2-p-toluoyloxy)ethyl chloride (5) to afford the respective 3'-toluoyloxy derivative 7 and not the anticipated 3'-O-[(p-toluoyloxy)ethyl]-dyphylline (6). Deacylation of 3a,b and 7 afforded 4ab and 1, respectively. Viral screening of selected compounds against HBV has been investigated.