Department of Chemistry, University Bayreuth, Universitaetsstr. 30, D-95440 Bayreuth, Germany.
Department of Microbial Drugs, Helmholtz Centre for Infection Research GmbH, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
Mar Drugs. 2021 Oct 19;19(10):583. doi: 10.3390/md19100583.
The sponge metabolite ancorinoside B was prepared for the first time in 16 steps and 4% yield. It features a β-d-galactopyranosyl-(1→4)-β-d-glucuronic acid tethered to a d-aspartic acid-derived tetramic acid. Key steps were the synthesis of a fully protected d-lactose derived thioglycoside, its attachment to a C-aldehyde spacer, functionalization of the latter with a terminal -(β-ketoacyl)-d-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 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 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.
海绵代谢产物锚定苷 B 经 16 步合成，产率为 4%。它的特点是β-d-半乳糖基-(1→4)-β-d-葡萄糖醛酸连接到天冬氨酸衍生的四氢酸上。关键步骤是全保护的 d-乳糖衍生的硫代糖苷的合成，其连接到 C-醛间隔物上，后者用末端-(β-酮酰基)-d-天冬氨酸官能化，以及碱性 Dieckmann 环化以同时进行伴随的全局脱保护，从而闭合吡咯烷-2,4-二酮环。锚定苷 B 表现出多种具有医学意义的生物学作用。当以低至 0.5μg/mL 的浓度应用时，它可以抑制癌症转移相关基质金属蛋白酶 MMP-2 和 MMP-9 的分泌，还可以将生物膜的生长抑制约 87%。这个浓度远低于其约 67μg/mL 的 MIC，因此不太可能诱导细菌耐药性。当以约 2μg/mL 的浓度应用时，它还可以导致预先形成的生物膜分散约 67%。因此，锚定苷 B 可能是控制一般医院、导管或关节假体感染的一个有趣的候选药物。
