Synthesis of the fungal macrolide berkeleylactone A and its inhibition of microbial biofilm formation. Issue 21 (11th May 2021)

• Record Type: Journal Article
• Authors: Schriefer, Manuel G.; Schrey, Hedda; Zeng, Haoxuan; Stadler, Marc; Schobert, Rainer
• Is Part Of: Organic & biomolecular chemistry. Volume 19:Issue 21(2021)
• Page Start: 4743
• Page End: 4751
• Publication Date: 2021-05-11
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d1ob00717c
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Berkeleylactone A was built up in 13 steps and 24% yield using a Wittig alkenation to close the macrocyle. It inhibited the formation of biofilms of Staphylococcus aureus and dispersed preformed biofilms of Candida albicans at subtoxic concentrations. Abstract : 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 Ph3 PCCO 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 .