51576-04-6Relevant articles and documents
Structure revision of isocereulide A, an isoform of the food poisoning emetic Bacillus cereus toxin cereulide
Ehling-Schulz, Monika,Hofmann, Thomas F.,Kranzler, Markus,Stark, Timo D.,Walser, Veronika
supporting information, (2021/05/31)
The emetic Bacillus cereus toxin cereulide presents an enormous safety hazard in the food industry, inducing emesis and nausea after the consumption of contaminated foods. Additional to cereulide itself, seven structurally related isoforms, namely the isocereulides A-G, have already been elucidated in their chemical structure and could further be identified in B. cereus contaminated food samples. The newly performed isolation of isocereulide A allowed, for the first time, 1D- and 2D-NMR spectroscopy of a biosynthetically produced isocereulide, revealing results that contradict previous assumptions of an L-O-Leu moiety within its chemical structure. By furthermore applying posthydrolytical dipeptide analysis, amino acid and α-hydroxy acid analysis by means of UPLC-ESITOF- MS, as well as MSn sequencing, the structure of previously reported isocereulide A could be corrected. Instead of the L-O-Leu as assumed to date, one L-O-Ile unit could be verified in the cyclic dodecadepsipeptide, revising the structure of isocereulide A to [(D-O-Leu-D-Ala-L-O-Val-L-Val)2(DO- Leu-D-Ala-L-O-Ile-L-Val)].
Synthesis and Structure-Activity Relationship Studies of C2-Modified Analogs of the Antimycobacterial Natural Product Pyridomycin
Kienle, Maryline,Eisenring, Patrick,Stoessel, Barbara,Horlacher, Oliver P.,Hasler, Samuel,Van Colen, Gwéna?lle,Hartkoorn, Ruben C.,Vocat, Anthony,Cole, Stewart T.,Altmann, Karl-Heinz
, p. 1105 - 1131 (2020/03/10)
A series of derivatives of the antimycobacterial natural product pyridomycin have been prepared with the C2 side chain attached to the macrocyclic core structure by a C-C single bond, in place of the synthetically more demanding enol ester double bond found in the natural product. Hydrophobic C2 substituents of sufficient size generally provide for potent anti-Mtb activity of these dihydropyridomycins (minimum inhibitory concentration (MIC) values around 2.5 μM), with several analogs thus approaching the activity of natural pyridomycin. Surprisingly, some of these compounds, in contrast to pyridomycin, are insensitive to overexpression of InhA in Mycobacterium tuberculosis (Mtb). This indicates that their anti-Mtb activity does not critically depend on the inhibition of InhA and that their overall mode of action may differ from that of the original natural product lead.
Discovery, Total Synthesis, and SAR of Anaenamides A and B: Anticancer Cyanobacterial Depsipeptides with a Chlorinated Pharmacophore
Brumley, David A.,Chen, Qi-Yin,Gunasekera, Sarath P.,Luesch, Hendrik,Paul, Valerie J.
supporting information, p. 4235 - 4239 (2020/06/27)
New modified depsipeptides and geometric isomers, termed anaenamides A (1a) and B (1b), along with the presumptive biosynthetic intermediate, anaenoic acid (2), were discovered from a marine cyanobacterium from Guam. Structures were confirmed by total synthesis. The alkylsalicylic acid fragment and the C-terminal α-chlorinated α,β-unsaturated ester are novelties in cyanobacterial natural products. Cancer cell viability assays indicated that the C-terminal unit serves as the pharmacophore and that the double-bond geometry impacts the cytotoxicity.
ANTIMICROBIAL PEPTIDES AND METHODS OF USE
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Paragraph 0009; 0139, (2020/02/14)
Cyclic depsipeptide-class molecules, referred to herein as persephacins (including analogs thereof), having similarities to aureobasidin A, are described. The persephacins have antimicrobial activity, such as antifungal activity against a diverse range of clinically -relevant fungal pathogens, antiprotozoan parasite activity, and antibacterial activity, and can be used for example in treatments of difficult-to-treat ocular fungal infections at lower concentrations than natamycin. The active compounds may be combined with a secondary compound in a composition.
Isolation, structure elucidation and biological evaluation of lagunamide D: A new cytotoxic macrocyclic depsipeptide from marine cyanobacteria
Luo, Danmeng,Putra, Masteria Y.,Ye, Tao,Paul, Valerie J.,Luesch, Hendrik
, (2019/02/19)
Lagunamide D, a new cytotoxic macrocyclic depsipeptide, was discovered from a collection of marine cyanobacteria from Loggerhead Key in the Dry Tortugas, Florida. An intramolecular ester exchange was observed, where the 26-membered macrocycle could contract to a 24-membered compound via acyl migration at the 1,3-diol unit, and the transformation product was named lagunamide D'. The planar structures of both compounds were elucidated using a combination of nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectroscopy (HRMS). The absolute configurations were determined on the basis of enantioselective analysis, modified Mosher's analysis, Kishi NMR database, and direct comparison with lagunamide A, a structure closely resembling lagunamide D. Lagunamides A and D displayed low-nanomolar antiproliferative activity against A549 human lung adenocarcinoma cells, while the structural transformation from the 26-membered lagunamide D macrocycle to the 24-membered ring structure for lagunamide D' led to a 9.6-fold decrease in activity. Lagunamide D also displayed potent activity in triggering apoptosis in a dose- and time-dependent manner. Further investigation on the mechanism of action of the lagunamide scaffold is needed to fully explore its therapeutic potential as an anticancer agent.
Total syntheses of cathepsin D inhibitory izenamides A, B, and C and structural confirmation of izenamide B
Lim, Changjin
, (2019/10/02)
The first total syntheses of izenamides A, B, and C, which are depsipeptides inhibitor of cathepsin D, were accomplished. In addition, the stereochemistry of izenamide B was confirmed by our syntheses. The key features of our synthetic route involve the avoidance of critical 2,5-diketopiperazine (DKP) formation and the minimization of epimerization during the coupling of amino acids for the target peptides.
Stereoselective Modification of N-(α-Hydroxyacyl)-glycinesters via Palladium-Catalyzed Allylic Alkylation
Horn, Alexander,Kazmaier, Uli
supporting information, p. 4595 - 4599 (2019/06/27)
N-(α-Hydroxyacyl)-glycinesters can be used as excellent nucleophiles in Pd-catalyzed allylic alkylation. The method allows for the stereoselective introduction of a wide range of side chains, including highly functionalized ones. Both diastereomers can be accessed through variation of the reaction conditions. Furthermore, the use of stannylated carbonates introduces vinylstannane motifs, which are eligible for subsequent C-C coupling reactions.
APRATYRAMIDE THERAPEUTIC AGENTS AND METHODS OF TREATMENT
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Page/Page column 46-48, (2019/06/11)
The invention is directed towards Apratyramide linear depsipeptide compounds, pharmaceutical compositions thereof, and methods of affecting wound healing, and methods of affecting the biological processes involved in wound healing (e.g., inflammation, cell proliferation, tissue granulation, remodeling of scar tissue, etc.).
Readily Accessible 1,2-Amino Ether Ligands for Enantioselective Intramolecular Carbolithiation
Guyon, Hélène,Boussonnière, Anne,Castanet, Anne-Sophie
, p. 4949 - 4957 (2017/05/12)
A new class of chiral 1,2-amino ether ligands, readily accessible from naturally occurring α-amino- or α-hydroxy acids, was found to provide high levels of both conversion and stereocontrol (up to 95:5 er) in intramolecular carbolithiation reactions, outperforming the benchmark ligand (?)-sparteine. The ligand could be used in a substoichiometric amount (0.25 equiv) without significant loss of enantioselectivity.
Dudawalamides A-D, Antiparasitic Cyclic Depsipeptides from the Marine Cyanobacterium Moorea producens
Almaliti, Jehad,Malloy, Karla L.,Glukhov, Evgenia,Spadafora, Carmenza,Gutiérrez, Marcelino,Gerwick, William H.
, p. 1827 - 1836 (2017/06/28)
A family of 2,2-dimethyl-3-hydroxy-7-octynoic acid (Dhoya)-containing cyclic depsipeptides, named dudawalamides A-D (1-4), was isolated from a Papua New Guinean field collection of the cyanobacterium Moorea producens using bioassay-guided and spectroscopic approaches. The planar structures of dudawalamides A-D were determined by a combination of 1D and 2D NMR experiments and MS analysis, whereas the absolute configurations were determined by X-ray crystallography, modified Marfey's analysis, chiral-phase GCMS, and chiral-phase HPLC. Dudawalamides A-D possess a broad spectrum of antiparasitic activity with minimal mammalian cell cytotoxicity. Comparative analysis of the Dhoya-containing class of lipopeptides reveals intriguing structure-activity relationship features of these NRPS-PKS-derived metabolites and their derivatives.
