Racemic Synthesis and Antiviral Evaluation of 4′(α)-Hydroxymethyl and 6′(α)-Methyl Substituted Apiosyl Nucleosides

Abstract

This article reports the novel synthesis of substituted apiosyl nucleosides. The key apiosyl intermediate 9 was constructed by sequential ozonolysis, reductions, and acetylation from the ester derivative 6. The nucleosides of uracil, thymine, cytosine, and adenine were synthesized using the glycosyl condensation procedure (silyated base and TMSOTf). The antiviral activities of the synthesized compounds against the HIV-1, HSV-1, HSV-2, and HCMV viruses were evaluated. The adenine derivative 26 showed weak anti-HIV activity (EC₅₀ = 10.1 μg/ml) without exhibiting any cytotoxicity up to a concentration of 100 μM.

Keywords:

• Antiviral agents
• substituted apiosyl nucleoside
• Ozonolysis

Acknowledgments

This work was supported by grant No. (R0120040001001302006) from the Basic Research Program of the Korea Science & Engineering Foundation.