Organic Letters
Letter
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against virulent H37Rv Mtb was consistent with the isolated
natural product with 1 possessing a MIC90 against Mtb H37Rv
of 312 31 nM (control: rifampicin MIC90 = 7 0.3 nM; see
In summary, we report here the first total synthesis of the
potent antimycobacterial cyclic depsipeptide natural product
ecumicin (1). This work now lays the foundation for the
generation of synthetic analogues of ecumicin in order to
generate SARs against the chaperone protein ClpC1, the
putative target of the natural product that is essential for
mycobacterial viability. This may ultimately stimulate the
discovery of ecumicin analogues as new TB drug leads that
operate through a novel mechanism of action to currently
employed therapies.
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ASSOCIATED CONTENT
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S
* Supporting Information
The Supporting Information is available free of charge on the
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(19) Wenschuh, H.; Beyermann, M.; Winter, R.; Bienert, M.;
Ionescu, D.; Carpino, L. A. Tetrahedron Lett. 1996, 37, 5483.
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288.
Experimental procedures for synthesis, antibacterial
screening, and characterization data and NMR spectra
AUTHOR INFORMATION
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Corresponding Author
ORCID
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We acknowledge Dr. Ian Luck (The University of Sydney) for
technical support for NMR spectroscopy and Dr. Nick
Proschogo (The University of Sydney) for technical support
for mass spectrometry. We also acknowledge the Australian
Postgraduate Award and the John A. Lamberton Research
Scholarship for PhD funding (P.M.E.H. and A.M.G.).
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