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

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

MDN-0104, an Antiplasmodial Betaine Lipid from <i>Heterospora chenopodii</i>

Bioassay-guided fractionation of the crude fermentation extract of <i>Heterospora chenopodii</i> led to the isolation of a novel monoacylglyceryltrimethylhomoserine (<b>1</b>). The structure of this new betaine lipid was elucidated by detailed spectroscopic analysis using one- and two-dimensional NMR experiments and high-resolution mass spectrometry. Compound <b>1</b> displayed moderate <i>in vitro</i> antimalarial activity against <i>Plasmodium falciparum</i>, with an IC₅₀ value of 7 μM. This betaine lipid is the first monoacylglyceryl­trimethyl­homoserine ever reported in the Fungi, and its acyl moiety also represents a novel natural 3-keto fatty acid. The new compound was isolated during a drug discovery program aimed at the identification of new antimalarial leads from a natural product library of microbial extracts. Interestingly, the related fungus <i>Heterospora dimorphospora</i> was also found to produce compound <b>1</b>, suggesting that species of this genus may be a promising source of monoacylglyceryltrimethylhomoserines