ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
0/0

Diversity Focused Semisyntheses of Tetronate Polyether Ionophores

preprint
submitted on 20.06.2019 and posted on 21.06.2019 by Shaoquan Lin, Han Liu, Esben B. Svenningsen, Christine Pedersen, Peter Nørby, Thomas Tørring, Thomas Poulsen
The polyether ionophores are complex natural products capable of transporting cations across biological membranes. Many family members possess highly potent antimicrobial activity and a few selected compounds have ability to target particularly aggressive cancer cells. Despite these interesting perspectives, a detailed understanding of the cellular mode-of-action of polyether ionophores is generally lacking. In principle, broad mapping of structure-activity relationships across several biological activities could provide mechanistic insights as well as identification of lead structures but access to structural diversity within the overall class is synthetically very challenging. In this manuscript, we demonstrate that novel polyether ionophores can be constructed by recycling components of highly abundant polyethers. We provide the first examples of synthetically incorporating halogen-functionalized tetronic acids as cation-binding groups into polyether ionophores and we identify analogs with strong anti-bacterial activity and minimal effects on mammalian cells.

Funding

Carlsbergfoundation (CF17-0800)

Independent research fund Denmark (6110-00600A)

History

Email Address of Submitting Author

thpou@chem.au.dk

Institution

Aarhus University

Country

Denmark

ORCID For Submitting Author

0000-0002-0763-9996

Declaration of Conflict of Interest

No conflicts of interest

Exports