Goondomycins A–H: Carbocyclic <i>ansa</i>-Polyketides from an Australian Pasture <i>Streptomyces</i> with Selective Activity against <i>Dirofilaria immitis</i>

A bioassay-guided chemical investigation of an Australian pasture-soil-derived <i>Streptomyces</i> sp. yielded the rare carbocyclic <i>ansa</i>-polyketide kendomycin (<b>1</b>) along with a series of new analogues, goondomycins A-H (<b>2</b>-<b>9</b>), featuring unprecedented carbo/heterocyclic scaffolds and chromophores, with structures assigned by detailed spectroscopic analysis, chemical and biochemical transformations, and biosynthetic considerations. Goondomycins B (<b>2</b>) and F (<b>7</b>) are noteworthy in being potent motility inhibitors of heartworm <i>Dirofilaria immitis</i> microfilaria (EC₅₀ 0.3 and 0.5 μM) and L4 larvae (EC₅₀ 1.4 and 1.8 μM), while exhibiting no significant antibacterial and antifungal activity or cytotoxicity to mammalian cells.