From the CH<sub>2</sub>Cl<sub>2</sub> extract of the Antarctic sponge <i>Dendrilla antarctica</i> we found spongian diterpenes, including previously reported aplysulphurin (<b>1</b>), tetrahydroaplysulphurin-1 (<b>2</b>), membranolide (<b>3</b>), and darwinolide (<b>4</b>), utilizing a CH<sub>2</sub>Cl<sub>2</sub>/MeOH extraction scheme. However, the extracts also yielded diterpenes bearing one or more methyl acetal functionalities (<b>5</b>-<b>9</b>), two of which are previously unreported, while others are revised here. Further investigation of diterpene reactivity led to additional new metabolites (<b>10</b>-<b>12</b>), which identified them as well as the methyl acetals as artifacts from methanolysis of aplysulphurin. The bioactivity of the methanolysis products, membranoids A-H (<b>5</b>-<b>12</b>), as well as natural products <b>1</b>-<b>4</b>, were assessed for activity against <i>Leishmania donovani</i>-infected J774A.1 macrophages, revealing insights into their structure/activity relationships. Four diterpenes, tetrahydroaplysulphurin-1 (<b>2</b>) as well as membranoids B (<b>6</b>), D (<b>8</b>), and G (<b>11</b>), displayed low micromolar activity against <i>L. donovani</i> with no discernible cytotoxicity against uninfected J774A.1 cells. Leishmaniasis is a neglected tropical disease that affects one million people every year and can be fatal if left untreated.