The synthesis of a series of 2-chloro- or 2-fluoro-9-(2-substituted-2-deoxy-β-D-arabinofuranosyl)adenines (4g-n) is described. New compounds were prepared from either 2-chloroadenosine or 2-fluoroadenosine by first blocking the 3'- and 5'-hydroxyls as the tetraisopropyldisiloxane derivatives. Activation of O-2' by formation of a triflate followed by nucleophilic displacement allowed introduction of various groups in the proper configuration at C-2'.Fluoride ion treatment then produced the deblocked nucleosides. All of the new compounds were evaluated as cytotoxic agents against L1210 and H.Ep.-2 cells and as antiviral agents against herpes simplex viruses 1 and 2 and vaccinia virus in culture. © 1988, American Chemical Society. All rights reserved.