Synthesis and evaluation of a series of 2'-O-acyl derivatives of 9-β-D-arabinofuranosyladenine as antiherpes agents

Article abstract of DOI:10.1021/jm00369a007

A series of four 9-(2-O-acyl-β-D-arabinofuranosyl)adenines was synthesized by acylation of 9-[3,5-bis-O-(tert-butyldimethylsilyl)-β-D-arabinofuranosyl]adenine followed by removal of the tert-butyldimethylsilyl groups under conditions (HOAc, teta-N-butyammonium fluoride) that prevented acyl migration. The four 2'-O-acyl derivatives showed activity in vitro against herpes type 1 viruses [virus ratings = 1.5-2.6; MIC₅₀ = 26-72 μg/mL (8.48-21.3 x 10^-5 M)]. The 2'-O-acetyl (5a) and 2'-O-valeryl derivatives were evaluated in a guinea pig model for genital herpes (herpes type 2); only 5a showed potent activity when given 6 or 24 h postinfection.