Non-geminal Aliphatic Dihalogenation Pattern in Dichlorinated Diaporthins from <i>Hamigera fusca</i> NRRL 35721

Abstract

Two new epimeric dihalogenated diaporthins, (9<i>R</i>^<i>*</i>)-8-methyl-9,11-dichlorodiaporthin (<b>2</b>) and (9<i>S</i>^<i>*</i>)-8-methyl-9,11-dichlorodiaporthin (<b>3</b>), have been isolated from the soil fungus <i>Hamigera fusca</i> NRRL 35721 alongside the known regioisomeric isocoumarin 8-methyl-11,11-dichlorodiaporthin (<b>1</b>). Their structures were elucidated by high-resolution mass spectrometry and NMR spectroscopy combined with molecular modeling. Compounds <b>1</b>–<b>3</b> are the first isocoumarins and the first halogenated metabolites ever reported from the <i>Hamigera</i> genus. The new compounds <b>2</b> and <b>3</b> display a non-geminal aliphatic dichlorination pattern unprecedented among known fungal dihalogenated aromatic polyketides. A bifunctional methyltransferase/aliphatic halogenase flavoenzyme is proposed to be involved in the biosynthesis of dichlorinated diaporthins <b>1</b>–<b>3</b>. These metabolites are weakly cytotoxic