Solid-Phase Synthesis of Guanine Derivatives with Four Diversity Elements via AgNO3-Mediated Guanidine Formation

Abstract

We constructed a guanine derivative library with four diversities through efficient solid-phase synthesis. In this reaction, thiourea was transformed into guanidine through a guanylation reaction using AgNO₃, and the guanine core was synthesized by cyclization using a base. After oxidation using mCPBA, several nucleophiles were substituted to construct 36 derivative libraries through solid-phase synthesis. The reaction involved 7 steps in total, showing a good yield of over 57–82%, but it also showed a difference in cyclization reaction selectivity between solid-phase synthesis and solvent-phase synthesis. We will use the synthesized chemical library to find hit compounds for various diseases.