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Stereoselective Oxidative Bioconjugation of Amino Acids and Oligopeptides to Aldehydes
Author(s) -
Tobiesen Henriette N.,
Leth Lars A.,
Iversen Marc V.,
Næsborg Line,
Bertelsen Søren,
Jørgensen Karl Anker
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202008513
Subject(s) - bioconjugation , chemistry , oligopeptide , amino acid , stereoselectivity , oxidizing agent , stereocenter , oxidative phosphorylation , combinatorial chemistry , oxidative coupling of methane , organic chemistry , biochemistry , peptide , catalysis , enantioselective synthesis
The first stereoselective, near‐equimolar, and metal‐free oxidative bioconjugation of amino acids and oligopeptides to aldehydes is presented. Based on a newly developed organocatalytic oxidative concept, the C‐terminal and side‐chain carboxylic acid functionalities of amino acids and oligopeptides are shown to couple in a stereoselective manner to α‐branched aldehydes catalyzed by a chiral primary amine and a quinone as oxidizing agent. The oxidative coupling generally proceeds in high yield. For aspartic acid, selective coupling of the side‐chain, or the C‐terminal carboxylic acid, is demonstrated depending on the protection strategy. The stereoselective, oxidative bioconjugation concept is extended to a series of oligopeptides where coupling to carboxylic acid functionalities is presented. Bioorthogonal linker molecules for further functionalization are obtained by merging the oxidative coupling strategy with the click concept. It is demonstrated that the configuration of the new stereocenter is determined exclusively by the organocatalyst.