Synthesis and Antiviral Evaluation of 4'-alkoxy Analogues of 9-(β-D-xylofuranosyl)adenine

Abstract

Background:

Motivated by the reported biological activity of 9-(β-D-xylofuranosyl)adenine (xylo-A), the synthesis of its 4'-alkoxy analogues was carried out.

Methods:

The starting material 9-(3-deoxy-β-D-glycero-pento–3-enofuranosyl)adenine (1) was prepared from adenosine. Compound 1 was converted to the 2',5'-bis-0–(tert-butyldimethylsilyl) derivative (2) and then to the N⁶-pivaloyl derivative (3). When 3 was reacted with meta- chloroperbenzoic acid in the presence of a series of alcohols, the β-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-I) 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-1 from that of xylo-A could be attributable to their inactivity.

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