Johannes Bingold, Thiago M Pereira, Johann E. Kratz, Abdulrahman Razzouk, Wibke Langenkamp, Ralf Weberskirch, Andreas Brunschweiger

Synthesis

DOI: 10.1055/a-2983-8624

Johannes Bingold, Thiago M Pereira, Johann E. Kratz, Abdulrahman Razzouk, Wibke Langenkamp, Ralf Weberskirch, Andreas Brunschweiger

Abstract

Isocyanide multicomponent reactions such as the Ugi fourcenter reaction are attractive for DNA-encoded library design because they allow for synthesizing diverse peptidomimetic and heterocyclic scaffolds from large numbers of simple and readily available starting materials. DNA amino acid conjugates with free N-terminus were solubilized in dry organic solvents with the help of an amphiphilic polyacrylate copolymer additive. This recently developed method allowed for reacting the DNA-tagged substrates with carbaldehydesubstituted arylcarboxylic acids via high-yielding and robust Ugi fourcenter three-component reaction to lactams and with cyclic ketones via Ugi four-center four-component reaction to diverse substituted peptidomimetic compounds that contain a central heterocyclic scaffold.Herein we discuss the scope and limitations of these two isocyanide multicomponent reaction strategies for DNA-encoded library synthesis.