| Summary: | The sponge metabolite ancorinoside B was prepared for the first time in 16 steps and 4% yield. It features a β-<span style="font-variant: small-caps;">d</span>-galactopyranosyl-(1→4)-β-<span style="font-variant: small-caps;">d</span>-glucuronic acid tethered to a <span style="font-variant: small-caps;">d</span>-aspartic acid-derived tetramic acid. Key steps were the synthesis of a fully protected <span style="font-variant: small-caps;">d</span>-lactose derived thioglycoside, its attachment to a C<sub>20</sub>-aldehyde spacer, functionalization of the latter with a terminal <i>N</i>-(β-ketoacyl)-<span style="font-variant: small-caps;">d</span>-aspartate, and a basic Dieckmann cyclization to close the pyrrolidin-2,4-dione ring with concomitant global deprotection. Ancorinoside B exhibited multiple biological effects of medicinal interest. It inhibited the secretion of the cancer metastasis-relevant matrix metalloproteinases MMP-2 and MMP-9, and also the growth of <i>Staphylococcus aureus</i> biofilms by ca 87% when applied at concentrations as low as 0.5 µg/mL. This concentration is far below its MIC of ca 67 µg/mL and thus unlikely to induce bacterial resistance. It also led to a 67% dispersion of preformed <i>S. aureus</i> biofilms when applied at a concentration of ca 2 µg/mL. Ancorinoside B might thus be an interesting candidate for the control of the general hospital, catheter, or joint protheses infections.
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