Total syntheses of prenylated isoflavones from Erythrina sacleuxii and their antibacterial activity
- The prenylated isoflavones 5-deoxyprenylbiochanin A (7-hydroxy-4'-methoxy-3'-prenylisoflavone) and erysubin F (7,4'-dihydroxy-8,3'-diprenylisoflavone) were synthesized for the first time, starting from mono-or di-O-allylated chalcones, and the structure of 5-deoxy-3'-prenylbiochanin A was corroborated by single-crystal X-ray diffraction analysis. Flavanones are key intermediates in the synthesis. Their reaction with hypervalent iodine reagents affords isoflavones via a 2,3-oxidative rearrangement and the corresponding flavone isomers via 2,3-dehydrogenation. This enabled a synthesis of 7,4'-dihydroxy-8,3'-diprenylflavone, a non-natural regioisomer of erysubin F. Erysubin F (8), 7,4'-dihydroxy-8,3'-diprenylflavone (27), and 5-deoxy-3'prenylbiochanin A (7) were tested against three bacterial strains and one fungal pathogen. All three compounds are inactive against Salmonella enterica subsp. enterica (NCTC 13349), Escherichia coli (ATCC 25922), and Candida albicans (ATCC 90028), with MIC values greater than 80.0 mu M. The diprenylatedThe prenylated isoflavones 5-deoxyprenylbiochanin A (7-hydroxy-4'-methoxy-3'-prenylisoflavone) and erysubin F (7,4'-dihydroxy-8,3'-diprenylisoflavone) were synthesized for the first time, starting from mono-or di-O-allylated chalcones, and the structure of 5-deoxy-3'-prenylbiochanin A was corroborated by single-crystal X-ray diffraction analysis. Flavanones are key intermediates in the synthesis. Their reaction with hypervalent iodine reagents affords isoflavones via a 2,3-oxidative rearrangement and the corresponding flavone isomers via 2,3-dehydrogenation. This enabled a synthesis of 7,4'-dihydroxy-8,3'-diprenylflavone, a non-natural regioisomer of erysubin F. Erysubin F (8), 7,4'-dihydroxy-8,3'-diprenylflavone (27), and 5-deoxy-3'prenylbiochanin A (7) were tested against three bacterial strains and one fungal pathogen. All three compounds are inactive against Salmonella enterica subsp. enterica (NCTC 13349), Escherichia coli (ATCC 25922), and Candida albicans (ATCC 90028), with MIC values greater than 80.0 mu M. The diprenylated natural product erysubin F (8) and its flavone isomer 7,4'-dihydroxy-8,3'diprenylflavone (27) show in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA, ATCC 43300) at MIC values of 15.4 and 20.5 mu M, respectively. In contrast, the monoprenylated 5-deoxy-3'-prenylbiochanin A (7) is inactive against this MRSA strain.…
Author details: | George KwesigaORCiDGND, Alexandra Kelling, Sebastian KerstingGND, Eric SperlichORCiDGND, Markus von Nickisch-RosenegkORCiD, Bernd SchmidtORCiDGND |
---|---|
DOI: | https://doi.org/10.1021/acs.jnatprod.0c00932 |
ISSN: | 0163-3864 |
ISSN: | 1520-6025 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/33170684 |
Title of parent work (English): | Journal of natural products |
Subtitle (English): | 5-deoxy-3′-prenylbiochanin A and erysubin F |
Publisher: | American Chemical Society |
Place of publishing: | Washington |
Publication type: | Article |
Language: | English |
Date of first publication: | 2020/11/10 |
Publication year: | 2020 |
Release date: | 2023/03/30 |
Volume: | 83 |
Issue: | 11 |
Number of pages: | 9 |
First page: | 3445 |
Last Page: | 3453 |
Funding institution: | transnational E-RARE grant `CCMCURE (DFG)European Commission [SFB958]; E-RARE [ERL 138397]; Canadian; Institutes for Health ResearchCanadian Institutes of Health Research; (CIHR) [PJT 153000]; the E-RARE grant `CCMCURE |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Chemie |
DDC classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
Peer review: | Referiert |