A Facile, Alternative Synthesis of 4‘-Thioarabinonucleosides and Their Biological Activities

Abstract

4‘-Thioarabinonucleosides, which are potential antiviral agents, were synthesized from d-glucose. 1,4-Anhydro-4-thioarabitol (8), which can be derived from diacetone glucose in nine steps, was subjected to Pummerer rearrangement after protection of the hydroxyl groups to give 1-O-acetyl-4-thioarabinose (11), which was condensed with nucleobases to give 4‘-thioarabinonucleosides. The 5-substituted-4‘-thioaraU (6a−e) derivatives showed anti-HSV-1 activity (ED₅₀ = 0.43−3.50 μg/mL). 4‘-ThioaraG (6h) and 2,6-diaminopurine 4‘-thioarabinonucleoside (4‘-thioaraDAP, 6g) showed antiviral activity against several herpes viruses and were particularly potent against human cytomegalovirus (0.010 and 0.022 μg/mL, respectively).