Synthesis of a Natural Product-Like Compound Collection through Oxidative Cleavage and Cyclization of Linear Peptides.

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.