Synthesis of the fungal macrolide berkeleylactone A and its inhibition of microbial biofilm formation.
Manuel G SchrieferHedda SchreyHaoxuan ZengMarc StadlerRainer SchobertPublished in: Organic & biomolecular chemistry (2022)
The fungal macrolide berkeleylactone A was synthesised in 13 steps and 24% yield using (R)-propylene oxide and an asymmetric Noyori hydrogenation of a β-ketoester to install the stereogenic centres. A domino addition-Wittig olefination of a 13-hydroxytetradecanal intermediate with the cumulated ylide Ph3PCCO closed the macrocyle by establishing the α,β-unsaturated ester group, necessary for the attachment of the sidechain thiol via a thia-Michael reaction. The synthetic berkeleylactone A inhibited the formation of Staphylococcus aureus biofilms and showed significant dispersive effects on preformed biofilms of Candida albicans by at least 45% relative to untreated controls at concentrations as low as 1.3 μg mL-1.
Keyphrases
- candida albicans
- biofilm formation
- staphylococcus aureus
- microbial community
- ionic liquid
- solid phase extraction
- cell wall
- gas chromatography mass spectrometry
- gas chromatography
- pseudomonas aeruginosa
- mass spectrometry
- escherichia coli
- cystic fibrosis
- tandem mass spectrometry
- methicillin resistant staphylococcus aureus