Antibacterial prenylated acylphloroglucinols from Psorothamnus fremontii

Authors: YU, QIAN - University Of Mississippi; RAO, RAVU RANGA - University Of Mississippi; XU, XIONG-MING - University Of Mississippi; GANJI, SURESH - University Of Mississippi; JACOB, MELISSA - University Of Mississippi; KHAN, SHABANA - University Of Mississippi; YU, BO-YANG - China Pharmaceutical University; LI, XING-CONG - University Of Mississippi

Submitted to: Organic Letters
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/8/2015
Publication Date: 10/15/2015
Publication URL: https://handle.nal.usda.gov/10113/62593
Citation: Yu, Q., Rao, R., Xu, X., Ganji, S., Jacob, M.R., Khan, S.I., Yu, B., Li, X. 2015. Antibacterial prenylated acylphloroglucinols from Psorothamnus fremontii. Organic Letters. 78:2748-2753. https://doi.org/10.1021/acs.jnatprod.5b00721.
DOI: https://doi.org/10.1021/acs.jnatprod.5b00721

Interpretive Summary: Discovery of new lead compounds from natural products for antibacterial drug development remains an important approach to combat antibiotic resistance. Bioassay-guided fractionation of the methanol extract of the native American plant Psorothamnus fremontii followed by structure elucidation afforded three new prenylated acylphloroglucinol derivatives, psorothatins A-C. Psorothatin C was the most active against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium with IC50 values in a range of 1.4-8.8 µg/mL. The first total synthesis of psorothatin C was achieved by a facile 4-step reaction sequence. This study has provided a novel chemically tractable natural product template for the synthesis of analogs with potentially improved antibacterial properties against drug resistant strains.

Technical Abstract: Antibacterial assay-guided fractionation of the methanol extract of the native American plant Psorothamnus fremontii followed by structure elucidation afforded three prenylated acylphloroglucinol derivatives, psorothatins A-C (1-3). They feature a unique a,ß-epoxyketone functionality and an a,ß-hydroxy-a,ß-unsatuated ketone structural moiety. The strong intramolecular hydrogen bonding in the molecules was evident by unusual proton-carbon correlations in the HMBC NMR spectrum. Compound 3 was active against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium with IC50s in a range of 1.4-8.8 µg/mL. The first total synthesis of 3 permits access to structural analogs with potentially improved antibacterial activities in the future.