Collect. Czech. Chem. Commun. 2004, 69, 1610-1630

Modified Tricyclic Analogues of Acyclovir. A Direct Alkynylation in the Fused Ring

Joanna Zeidler

Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland


Two types of new 7-alkynylated tricyclic analogues (3,9-dihydro-5H-imidazo[1,2-a]purin-9-ones) of acyclovir differing by the presence of N-5 substituent, a temporary 2-(4-nitrophenyl)ethyl or a permanent 3-hydroxypropyl were obtained by a Sonogashira coupling. 7-Alk-1-ynyl-5-(3-acetoxypropyl) compounds (19a-19d, 21a-21c) were efficiently prepared from 7-iodo, 7-iodo-6-methyl precursors 12 and 11, respectively, and deprotected while the products with unsubstituted N-5 were unstable (e.g. 17). Iodide 12 was generally less reactive than 11 and underwent a preferable reduction (48%) to deiodinated 8 when coupled with ethynyltrimethylsilane.

Keywords: Acyclovir; Alkynes; Fused purines; Acyclic nucleosides; Sonogashira reaction; Mitsunobu alkylation; NH protecting groups; Reductive deiodination.

References: 32 live references.