Metabolites toxic to spruce budworm from balsam fir needle endophytes

The bioactive constituents of extracts of three strains of balsam fir endophytic fungi, reported to cause reduced growth rate and mortality of spruce budworm larvae, have been isolated and characterized. Bioassay-directed fractionation has resulted in the identification of heptelidic acid, 1,5a,6,7,8,9a-hexahydro-6-(1-methylethyl)-1-oxo-spiro[2-benzoxepin-9(3H),2′oxirane]-4-carboxylic acid ( 1 ), and two new analogues, heptelidic acid chlorohydrin ( 2 ), and hydroheptelidic acid ( 3 ), as the biologically active components of ? Phyllosticta sp. strain 76. The active component of Hormonema dematioides strains 53 and 143 was identified as (+)rugulosin ( 4 ), an anthraquinone previously reported to exhibit a wide spectrum of biological activity. This is the first report of the identification of toxins from fungal endophytes of woody plants.