Niversitaetsstr. 30, D-95440 Bayreuth, Germany; [email protected] (K.J.S.
Niversitaetsstr. 30, D-95440 Bayreuth, Germany; [email protected] (K.J.S.); [email protected] (S.I.B.); [email protected] (N.O.) Department of Microbial Drugs, Helmholtz Centre for Infection Study GmbH, Inhoffenstrasse 7, 38124 Braunschweig, Germany; haoxuan.zeng@Diversity Library Description helmholtz-hzi.de (H.Z.); [email protected] (H.S.) Correspondence: [email protected]; Fax: 49-(0)921-Citation: Soliga, K.J.; B , S.I.; Oberhuber, N.; Zeng, H.; Schrey, H.; Schobert, R. Synthesis and Bioactivity of Ancorinoside B, a Marine Diglycosyl Tetramic Acid. Mar. Drugs 2021, 19, 583. https://doi.org/ ten.3390/md19100583 Academic Editor: Lyndon West Received: 6 October 2021 Accepted: 15 October 2021 Published: 19 OctoberAbstract: The sponge metabolite ancorinoside B was ready for the very first time in 16 measures and four yield. It features a -D-galactopyranosyl-(14)–D-glucuronic acid tethered to a D-aspartic acid-derived tetramic acid. Important methods had been the synthesis of a completely protected D-lactose derived thioglycoside, its attachment to a C20 -aldehyde spacer, functionalization of the latter with a terminal N-(-ketoacyl)-D-aspartate, plus a simple Dieckmann cyclization to close the pyrrolidin-2,4-dione ring with concomitant global deprotection. Ancorinoside B exhibited many biological effects of medicinal interest. It inhibited the secretion with the cancer metastasis-relevant matrix metalloproteinases MMP-2 and MMP-9, as well as the development of Staphylococcus aureus biofilms by ca 87 when applied at concentrations as low as 0.5 /mL. This concentration is far beneath its MIC of ca 67 /mL and hence unlikely to induce bacterial resistance. Additionally, it led to a 67 dispersion of preformed S. aureus biofilms when applied at a concentration of ca two /mL. Ancorinoside B might thus be an fascinating candidate for the handle of the general hospital, catheter, or joint protheses infections. Keywords and phrases: glycosyl tetramic acid; ancorinoside B; marine sponge metabolite; microbial biofilm inhibitor; MMP inhibitor1. Introduction Tetramic acids with glycosylated 3-acyl sidechains happen in nature as metabolites of bacteria, fungi/molds, and sponges. Their bioactivities span a broad spectrum, which includes antifungal, antibacterial, cytotoxic, and particular protein inhibitory effects [1]. They differ significantly in terms of structural complexity, culminating in compounds such as the aflastatins [5], that are fraught with functional groups and stereogenic centers. Nonetheless, structural intricacy just isn’t a prerequisite for biological activity. The YC-001 Endogenous Metabolite ancorinosides A (1; Figure 1) have been isolated from marine sponges Ancorina sp. and Penares sollasi by the groups of Ohta et al. [6] and Fusetani et al. [7]. They had been discovered to inhibit membrane-type matrix metalloproteinases (MT1-MMPs) that are relevant for tumor development and metastasis, and feature unadorned alkyl tethers and either a terminal -D-glucopyranosyl-(14)-D -galacturonic acid (for 1 and four) or a – D -galactopyranosyl-(14)– D -glucuronic acid residue (for 2 and three). Previously, we reported syntheses of ancorinosides A (1) [8] and D (four) [9], beginning from D-glucose and D-galactose creating blocks, in addition to a D-aspartic acid ester. As this idea was not applicable for the disaccharide motif of ancorinosides B (2) and C (three), we now developed an option method beginning with low-cost D-lactose.Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliati.