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Syntheses of Thailandepsin?B Pseudo-Natural Products: Access to New Highly Potent HDAC Inhibitors via Late-Stage Modification.

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.

SUBMITTER: Brosowsky J

PROVIDER: S-EPMC7756392 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Syntheses of Thailandepsin B Pseudo-Natural Products: Access to New Highly Potent HDAC Inhibitors via Late-Stage Modification.

Brosowsky Jana J Lutterbeck Monika M Liebich Amelie A Keller Manfred M Herp Daniel D Vogelmann Anja A Jung Manfred M Breit Bernhard B

Chemistry (Weinheim an der Bergstrasse, Germany) 20201103 69

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 ...[more]

PMID: 32725698

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