Multicomponent Synthesis of C(8)‐Substituted Purine Building Blocks of Peptide Nucleic Acids from Prebiotic Compounds

Abstract

Abstract We have explored the reaction of a three‐components mixture of aminomalononitrile, urea and α‐amino acid methyl esters for the multicomponent synthesis substituted purines resembling PNA's building blocks. 2,6‐diamino‐purines, 6‐amino‐3,9‐dihydro‐2H‐purin‐2‐one (iso‐guanines), and 3,9‐dihydro‐6H‐purin‐6‐one derivatives, selectively decorated at C(8)‐position of the purine ring with different amino acid residues, were obtained from acceptable to good yields. The regio‐selectivity of the transformation was controlled by the use of urea in the ternary mixture and by the annulation agent involved in the ring‐closure of amino‐imidazole carbonitrile intermediates. Solvent free conditions, microwave irradiation and simple one‐carbon containing reagents further satisfied the major requirement of atom economy and sustainable chemistry. Due to the prebiotic nature of the three‐components mixture and of annulation agents, it also embodies the possibility for the synthesis of novel PNAs bearing purine nucleobases decorated at C(8)‐position of the imidazole ring as alternative RNA analogues in molecular evolution.

Keywords

• Multicomponent Synthesis
• Peptide Nucleic Acid
• C(8)-substituted purines
• PNA's building block
• Prebiotic synthesis