Solid-Phase Synthesis of 4(5),10,50-Trisubstituted 2,40-Biimidazoles

摘要

Amethod for the synthesis of libraries of 4(5),10,50-trisubstituted 2,40-biimidazoles on a solid support was developed.1 A trivalent scaffold, 2-(50-amino-4(5)-formyl-1H,10H-2,40-biimidazol-10-yl)acetic acid, was first prepared in solution by a two-step synthesis from ethyl adenin-9-ylacetate and bromomalonaldehyde. The product was coupled to an amino acid loadedWang resin and the formyl group was subsequently derivatized either by reductive amination, oximation, or hydrazone formation. The 50-amino group of the resin-bound biimidazole was then acylated and the products were finally released from the resin and purified. 50-Amino-2,40-biimidazole offers a scaffold for lead compounds of drug discovery, possibly useful in finding leads for protein kinase inhibitors.