Semisynthetic Tetramate-Containing Fungal Metabolites with Activity against <i>Trichomonas vaginalis</i> and <i>Mycoplasma genitalium</i>

Tetramic acid-containing natural products are well known for their promising biological activity against various diseases. In our previous study, we reported fungal-derived tetramic acid-containing natural products with activity against <i>Trichomonas vaginalis</i>. Here, we demonstrate that <i>Mycoplasma genitalium</i> is also highly susceptible to this chemotype and we uncovered the initial structure activity relationships on disparate tetramate chemotypes in phomasetin (<b>6</b>) and pyrrolocin A (<b>10</b>). Further, <b>6</b> and <b>10</b> were modified using "click" chemistry to re-engineer bioactivity. Compounds <b>6</b> and <b>10</b> hold promise as a pipeline-diversifying chemotype for promising leads against <i>T</i>. <i>vaginalis</i> and <i>M</i>. <i>genitalium</i>.