Synthesis of a Natural Product‐Like Compound Collection through Oxidative Cleavage and Cyclization of Linear Peptides |
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Authors: | Dr Rico Petersen Dr Sebastian T Le?Quement Prof?Dr Thomas E Nielsen |
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Institution: | 1. Department of Chemistry, Technical University of Denmark, Kemitorvet, Building 201, 2800 Kgs. Lyngby (Denmark);2. Singapore Centre on Environmental Life Sciences Engineering Nanyang Technological University, 637551 Singapore (Singapore) |
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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. |
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Keywords: | drug discovery heterocycles molecular diversity peptides solid‐phase synthesis |
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