Background: Motivated by the reported biological activity of 9-(beta-D-xylofuranosyl)adenine (xylo-A), the synthesis of its 4'-alkoxy analogues was carried out.
Methods: The starting material 9-(3-deoxy-beta-D-glycero-pento-3-enofuranosyl)adenine (1) was prepared from adenosine. Compound 1 was converted to the 2',5'-bis-O-(tert-butyldimethylsilyl) derivative (2) and then to the N(6)-pivaloyl derivative (3). When 3 was reacted with meta-chloroperbenzoic acid in the presence of a series of alcohols, the beta-D-isomer of the respective 4'-alkoxy derivative was obtained exclusively in high yield. Deprotection of these products led to the isolation of the desired 4'alkoxy analogues (8a-l) of xylo-A.
Results: Antiviral evaluation revealed that none of these analogues showed inhibitory activity against a wide variety of DNA and RNA viruses.
Conclusions: We assume that conformational difference of the sugar moiety of 8a-l from that of xylo-A could be attributable to their inactivity.