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Updated: Apr 9, 2026

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
Acid-Catalyzed Cycloaddition of Guanines with TMOP: A Unified Strategy for Synthesizing Tricyclic Acyclovir Analogues
Zhuo-Yue Jia1, Bin Wu1, Wen-Wu Sun1
1School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China.
Abstract:
This article describes an efficient acid-catalyzed cyclization strategy for constructing the tricyclic pyrimido[1,2-a]purin-10(3H)-one scaffold via the reaction of guanine derivatives with 1,1,3,3-tetramethoxypropane (TMOP) catalyzed by 2,4,5-trifluorobenzoic acid. The method features mild conditions, eliminates the need for hydroxyl protection, and exhibits excellent functional-group tolerance, making it applicable to the late-stage structural diversification of various nucleosides, nucleotides, and oligonucleotides. Using the antiviral drug acyclovir and an azide-containing guanosine derivative as model substrates, we successfully synthesized a tricyclic acyclovir analogue in 81% yield and an M1G-containing oligonucleotide in 40% yield. This protocol provides a general, convenient, and efficient experimental approach for synthesizing this class of potentially bioactive tricyclic nucleoside analogues. © 2026 Wiley Periodicals LLC. Basic Protocol 1: Synthesis of tricyclic acyclovir analogue Basic Protocol 2: Synthesis of M1G-containing oligonucleotide.
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