Reconstructive Approach to the Regiospecific Synthesis of N 9‐Alkylated Purines

A regiospecific synthesis of N 9‐alkylated purines as novel acyclic nucleosides was developed. This approach is based on reconstructive methodology involving the construction of a target heterocyclic scaffold on a readily available 5‐aminotetrazole moiety, which is subsequently cleaved under reducti...

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Bibliographic Details
Published in:European journal of organic chemistry 2024-08, Vol.27 (32)
Main Authors: Savateev, Konstantin V., Gazizov, Denis A., Slepukhin, Pavel A., Ulomsky, Evgeniy N., Rusinov, Vladimir L.
Format: Article
Language:English
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Summary:A regiospecific synthesis of N 9‐alkylated purines as novel acyclic nucleosides was developed. This approach is based on reconstructive methodology involving the construction of a target heterocyclic scaffold on a readily available 5‐aminotetrazole moiety, which is subsequently cleaved under reductive conditions due to azido‐tetrazole tautomerism. It appeared that the rate of reduction for the azide fragment in 6‐nitro‐7‐alkylaminotetrazolo[1,5‐ a ]pyrimidines is much greater than the rate of nitro group reduction. Treatment of these heterocycles with hydrogen over a palladium catalyst resulted in the formation of triaminopyrimidines in excellent yields through the reduction of both the azide and nitro group. Triaminopyrimidines were transformed into the desired N 9‐alkylated purines, and an analog of the marketed drug penciclovir was synthesized by the developed method.
ISSN:1434-193X
1099-0690
DOI:10.1002/ejoc.202400426