Total synthesis and antibacterial evaluation of Empetroxepins A and B and related analogs

Total synthesis and antibacterial evaluation of Empetroxepins A and B and related analogs

[Display omitted] Empetroxepins A and B, which are 10,11-dihydrodibenz[b,f]oxepins produced by the Black Crowberry (Empetrum nigrum), displayed weak anti-tubercular activity upon isolation, but have not been explored for antibiotic activity despite their molecular similarity to other phenolic antiba...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters Vol. 75; p. 128955
Main Authors: Murphy, Kyle E., Thacher, Marcia K., Young, Erin C., Mojik, Veronika, Wolfe, Amanda L.
Format: Journal Article
Language:English
Published: Elsevier Ltd 01-11-2022
Subjects:
Antibiotic
Empetroxepin A
Empetroxepin B
Natural products
Selective demethylation
TSB
SAR
DMSO
MIC
TMSI
Bn
SA
DCM
Et
BS
Antibiotic
THF
Natural products
Me
Ph
TMS
Empetroxepin A
EC
Empetroxepin B
Selective demethylation
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Summary:[Display omitted] Empetroxepins A and B, which are 10,11-dihydrodibenz[b,f]oxepins produced by the Black Crowberry (Empetrum nigrum), displayed weak anti-tubercular activity upon isolation, but have not been explored for antibiotic activity despite their molecular similarity to other phenolic antibacterial natural products. Herein we detail the first total synthesis of Empetroxepins A and B via a selective demethylation strategy and antibacterial structure activity relationship (SAR) study of the natural products and related analogs. Empetroxepin A was found to be weakly active against susceptible strains of Staphylococcus aureus (SA) and Bacillus subtilis (BS) with a minimum inhibitory concentration (MIC) of 256 μg/mL against both bacteria, whereas Empetroxepin B was found to be weakly active against only BS (MIC = 256 μg/mL). Neither natural product was active against Escherichia coli (EC). Antibiotic activity was improved through derivatization of the 10,11-dihydrodibenz[b,f]oxepin core with the best compound of the SAR series, 9-chloro-10,11-dihydrodibenzo[b,f]oxepine-2,3,4-triol, having MICs of 8 μg/mL, 16 μg/mL, and 256 μg/mL against SA, BS, and EC respectively.
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ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2022.128955