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Syntheses of Thailandepsin B Pseudo‐Natural Products: Access to New Highly Potent HDAC Inhibitors via Late‐Stage Modification
Author(s) -
Brosowsky Jana,
Lutterbeck Monika,
Liebich Amelie,
Keller Manfred,
Herp Daniel,
Vogelmann Anja,
Jung Manfred,
Breit Bernhard
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202002449
Subject(s) - hydroamination , moiety , natural product , rhodium , chemistry , combinatorial chemistry , allylic rearrangement , catalysis , stereochemistry , organic chemistry
Abstract New Thailandepsin B pseudo‐natural products have been prepared. Our synthetic strategy offers the possibility to introduce varying warheads via late stage modification. Additionally, it gives access to the asymmetric branched allylic ester moiety of the natural product in a highly diastereoselective manner applying rhodium‐catalyzed hydrooxycarbonylation. The newly developed pseudo‐natural products are extremely potent and selective HDAC inhibitors. The non‐proteinogenic amino acid d ‐norleucine was obtained enantioselectively by a recently developed method of rhodium‐catalyzed hydroamination.