Regio‐ and Stereoselective Epoxidation and Acidic Epoxide Opening of Antibacterial and Antiplasmodial Chlorotonils Yield Highly Potent Derivatives
Abstract: The rise of antimicrobial resistance poses a severe threat to public health. The natural product chlorotonil was identified as a new antibiotic targeting multidrug resistant Gram‐positive pathogens and Plasmodium falciparum. Although chlorotonil shows promising activities, the scaffold is highly lipophilic and displays potential biological instabilities. Therefore, we strived towards improving its pharmaceutical properties by semisynthesis. We demonstrated stereoselective epoxidation of chlorotonils and epoxide ring opening in moderate to good yields providing derivatives with significantly enhanced solubility. Furthermore, in vivo stability of the derivatives was improved while retaining their nanomolar activity against critical human pathogens (e.g. methicillin‐resistant Staphylococcus aureus and P. falciparum). Intriguingly, we showed further superb activity for the frontrunner molecule in a mouse model of S. aureus infection.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Regio‐ and Stereoselective Epoxidation and Acidic Epoxide Opening of Antibacterial and Antiplasmodial Chlorotonils Yield Highly Potent Derivatives ; day:13 ; month:06 ; year:2022 ; extent:1
Angewandte Chemie / International edition. International edition ; (13.06.2022) (gesamt 1)
- Urheber
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Hofer, Walter
Oueis, Emilia
Fayad, Antoine Abou
Deschner, Felix
Andreas, Anastasia
de Carvalho, Laìs Pessanha
Hüttel, Stephan
Bernecker, Steffen
Pätzold, Linda
Morgenstern, Bernd
Zaburannyi, Nestor
Bischoff, Markus
Stadler, Marc
Held, Jana
Herrmann, Jennifer
Müller, Rolf
- DOI
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10.1002/anie.202202816
- URN
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urn:nbn:de:101:1-2022061415033832818591
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:23 MESZ
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Beteiligte
- Hofer, Walter
- Oueis, Emilia
- Fayad, Antoine Abou
- Deschner, Felix
- Andreas, Anastasia
- de Carvalho, Laìs Pessanha
- Hüttel, Stephan
- Bernecker, Steffen
- Pätzold, Linda
- Morgenstern, Bernd
- Zaburannyi, Nestor
- Bischoff, Markus
- Stadler, Marc
- Held, Jana
- Herrmann, Jennifer
- Müller, Rolf
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