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Published on: July 16, 2016
Non-geminal Aliphatic Dihalogenation Pattern in Dichlorinated Diaporthins from Hamigera fusca NRRL 35721
Celso Almeida1, Ignacio Pérez-Victoria1, Víctor González-Menéndez1
1Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Parque Tecnológico de Ciencias de la Salud , Avenida del Conocimiento 34 , 18016 Armilla , Granada , Spain.
Abstract:
Two new epimeric dihalogenated diaporthins, (9 R *)-8-methyl-9,11-dichlorodiaporthin (2) and (9 S *)-8-methyl-9,11-dichlorodiaporthin (3), have been isolated from the soil fungus Hamigera fusca NRRL 35721 alongside the known regioisomeric isocoumarin 8-methyl-11,11-dichlorodiaporthin (1). Their structures were elucidated by high-resolution mass spectrometry and NMR spectroscopy combined with molecular modeling. Compounds 1-3 are the first isocoumarins and the first halogenated metabolites ever reported from the Hamigera genus. The new compounds 2 and 3 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 1-3. These metabolites are weakly cytotoxic.
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