Synthesis of a natural product-like compound collection through oxidative cleavage and cyclization of linear peptides

• Main Authors: Petersen, Rico, Le Quement, Sebastian T., Nielsen, Thomas E.
• Format: Article
• Language: English
• Published: 2015
• Subjects: DRNTU::Science::Chemistry::Organic chemistry::Oxidation
• Online Access: https://hdl.handle.net/10356/103931; http://hdl.handle.net/10220/24634
• Institution: Nanyang Technological University

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 stereochemically diverse compounds was generated, and selected compounds were elaborated into isoform-selective metalloprotease inhibitors.