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Synthesis of a Natural Product‐Like Compound Collection through Oxidative Cleavage and Cyclization of Linear Peptides
Author(s) -
Petersen Rico,
Le Quement Sebastian T.,
Nielsen Thomas E.
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201405747
Subject(s) - natural product , combinatorial chemistry , chemistry , solid phase synthesis , monomer , peptide synthesis , peptide , cleavage (geology) , amino acid , oxidative phosphorylation , oxidative cleavage , stereochemistry , biochemistry , organic chemistry , biology , catalysis , paleontology , fracture (geology) , polymer
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.