Spiromastixones A–O, Antibacterial Chlorodepsidones from a Deep-Sea-Derived <i>Spiromastix</i> sp. Fungus

Fifteen new depsidone-based analogues named spiromastixones A–O (<b>1</b>–<b>15</b>) were isolated from the fermentation broth of a deep-sea <i>Spiromastix</i> sp. fungus. Their structures were elucidated on the basis of extensive NMR and mass spectroscopic analysis in association with chemical conversion. Spiromastixones A–O are classified into two subtypes based on the orientation of ring C relative to ring A, while the <i>n</i>-propyl substituents on rings A and C are rarely seen in natural products. Most analogues are substituted by various numbers of chlorine atoms. All compounds exhibited significant inhibition against Gram-positive bacteria including <i>Staphylococcus aureus</i>, <i>Bacillus thuringiensis</i>, and <i>Bacillus subtilis</i> with MIC values ranging from 0.125 to 8.0 μg/mL. In addition, compounds <b>6</b>–<b>10</b> displayed potent inhibitory effects against methicillin-resistant bacterial strains of <i>S. aureus</i> (MRSA) and <i>S. epidermidis</i> (MRSE), while <b>10</b> also inhibited the growth of the vancomycin-resistant bacteria <i>Enterococcus faecalis</i> and <i>E. faecium</i> (VRE). The structure–activity relationships are discussed