Petersen, Rico1; Le Quement, Sebastian Thordal1; Nielsen, Thomas Eiland3
1 Department of Chemistry, Technical University of Denmark2 Organic Chemistry, Department of Chemistry, Technical University of Denmark3 Department of Organic Chemistry, Technical University of Denmark
Massive efforts in molecular library synthesis have strived for the development of synthesis methodology which systematically delivers natural product-like compounds of high spatial complexity. Herein, we present a conceptually simple approach that builds on the power of solid-phase peptide synthesis to assemble precursor peptides (oligomers) designed to undergo oxidative cascade reactions. By harnessing the structural side-chain diversity and inherent stereochemical features offered by readily available amino acids (monomers), a proof-of-concept collection of 54 skeletally and stereochem- ically diverse compounds was generated, and selected com- pounds were elaborated into isoform-selective metalloprotease inhibitors.