title: Synthesis of a natural product-like compound collection through oxidative cleavage and cyclization of linear peptides.
abstract: 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.
authors.affiliation: Department of Chemistry, Technical University of Denmark, Kemitorvet, Building 201, 2800 Kgs. Lyngby (Denmark).
authors.forename: Rico
authors.initials: R
authors.lastname: Petersen
authors.forename: Sebastian T
authors.initials: ST
authors.lastname: Le Quement
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Nielsen
mesh_terms: D000147:Acids, Heterocyclic; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D055808:Drug Discovery / Q000379:methods*; D008958:Models, Molecular; D010455:Peptides / Q000378:metabolism*
chemical_list: D000147:Acids, Heterocyclic; D001688:Biological Products; D010455:Peptides
keywords: drug discovery; heterocycles; molecular diversity; peptides; solid-phase synthesis