Synthesis of Novel Acyclonucleosides Analogs of Pyridothienopyrimidine as Antiviral Agents

Abstract

Nucleoside analogs of pyridothienopyramidines were prepared by condensing the sodium salt 2a,b with an acyclic side chain in the form of acetylated haloalkoxyalcohol, and subsequent removal of the protecting acetyl group in ammonia/methanol afforded 4a,b. The O-tosyl derivative of 4a could then be modified to azido- and amino derivatives. Reaction of the sodium salt of 2b with halo-ether, benzyl halo-ether and/or halo-thioether gave N- and S-alkylated products, 8 and 9, respectively. Coupling of 10 with the sodium salt of 2a,b gave the corresponding dioxolane derivatives 11, 13, and 14, which were treated with 80% acetic acid at room temperature to give diols 12, 15, and 16. Treatment of 16 with tosyl chloride afforded the ditosylate 17 and this could then be modified to diazido and diamino derivatives. Some of the products were screened for their biological activity.

Keywords:

• Acyclonucleosides
• Pyridothienopyrimidines
• Alkylation

DANIDA and Danish Ministry of Foreign Affairs are gratefully acknowledged for financial support through the project “Development of New Drugs against Hepatitis” at Monoufiya University, and Prof. E. B. Pedersen, Chemistry Institute, Odence University, Denmark for recording spectra and Microanalysis.