Organic Letters
Letter
mediated oxidative disulfide bond formation to generate the
versatile cyclic peptide carboxylic acid 2 and introduction of the
4-hydroxystyrylamide late in the synthesis via a Grieco
elimination procedure. The utility of this methodology was
further illustrated with the synthesis of several gombamide A
derivatives. The natural product and four analogs (2, 24, 27,
and 29) were shown to be devoid of Na+/K+-ATPase activity at
10 μM. Finally, these five compounds were not cytotoxic
against a panel of cancer cell lines at 10 μM, which should
encourage exploration of this chemotype for nononcology
pharmacological applications.
Scheme 3. Synthesis of Gombamide A (1) and Derivative 24
ASSOCIATED CONTENT
* Supporting Information
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S
The Supporting Information is available free of charge on the
Description of the detailed experimental procedures and
AUTHOR INFORMATION
Corresponding Author
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We thank the University of Houston for financial support and
the National Cancer Institute for testing the compounds in the
60 cell line assays.
phenethylamine derivatives were prepared (Scheme 4).
Compound 27 was obtained by coupling carboxylic acid 2
Scheme 4. Synthesis of Gombamide A Derivatives 27 and 29
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