First syntheses of the biologically active fungal metabolites pestalotiopsones A, B, C and FElectronic supplementary information (ESI) available: General experimental conditions and copies of NMR data for all synthesised compounds, along with analytical data for the synthesised natural products are available online. See DOI: 10.1039/c2ob26904j

A synthetic approach accessing the pestalotiopsones, fungal chromones possessing a rare skeletal subtype, is reported for the first time. The synthesis of pestalotiopsone A ( 1 ) has been achieved in 7 linear steps (28%), from commercially available 3,5-dimethoxybenzoic acid and subsequently the first syntheses of pestalotiopsone B ( 2 ), C ( 3 ) and F ( 4 ) were performed utilising this chemistry. The key steps include a newly described homologation of a substituted benzoic acid to afford phenylacetate derivatives utilising Birch reductive alkylation conditions, a microwave mediated chromanone formation proceeding through an oxa-Michael cyclisation, and an IBX induced dehydrogenation to the desired chromone skeleton. The synthetic natural products were completely characterised for the first time, confirming their structures and their biological activities evaluated against a panel of bacterial pathogens. The pestalotiopsones are bioactive compounds isolated from the endophytic fungus, Pestalotiopsis sp., associated with the Chinese traditional medicinal plant, Rhizophora mucronata . The first syntheses of pestalotiopsones A, B, C and F are described.