Marine Natural Occurring 2,5-Diketopiperazines: Isolation, Synthesis and Optical Properties (original) (raw)
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Isolation and Structure Elucidation of Bioactive Secondary Metabolites from Marine Sponges
docserv.uni-duesseldorf.de
Cytotoxic cyclic peptide……………………………………………………..….170 Biosynthesis of peptides………………………………………………………...171 Relationship between structures and cytotoxic activities of callyaerins …….....174 4.2. Metabolites isolated from the sponge Diacarnus megaspinorhabdosa…...…174 Cytotoxic norterpene peroxides…………………………………………………174 Proposed biosynthesis of terpene peroxides……………………..…………...…175 Mechanism of the antimalarial activity of cyclic peroxides…………………….177 Structure activity relationship of norterpene cyclic peroxides…………….……178 Indole, phenolic and nucleoside derivatives.………………………………...…179 Mechanism of action of nucleoside analogs.
Marine Drugs, 2011
While investigating the cytotoxic activity of the methanol extract of an Australian marine sponge Stelletta sp. (Demospongiae), a new diketopiperazine, cyclo-(4-S-hydroxy-R-proline-R-isoleucine) (1), was isolated together with the known bengamides; A (2), F (3), N (4), Y (5), and bengazoles; Z (6), C 4 (7) and C 6 (8). The isolation and structure elucidation of the diketopiperazine (1), together with the activity of 1-8 against a panel of human and mammalian cell lines are discussed.
Marine Drugs
The Persian Gulf is a unique and biologically diverse marine environment dominated by invertebrates. In continuation of our research interest in the chemistry and biological activity of marine sponges from the Persian Gulf, we selected the excavating sponge Cliona celata for detailed metabolome analyses, in vitro bioactivity screening, and chemical isolation studies. A UPLC-MS/MS (MS2) molecular-networking-based dereplication strategy allowed annotation and structural prediction of various diketopiperazines (DKPs) and etzionin-type diketopiperazine hydroxamates (DKPHs) in the crude sponge extract. The molecular-networking-guided isolation approach applied to the crude extract afforded the DKPH etzionin (1) and its two new derivatives, clioetzionin A (2) and clioetzionin B (3). Another new modified DKP (4) was identified by MS/MS analyses but could not be isolated in sufficient quantities to confirm its structure. The chemical characterization of the purified DKPHs 1–3 was performed ...
Acanthocyclamine A From the Indonesian Marine Sponge Acanthostrongylophora ingens
Australian Journal of Chemistry, 2014
A new 3-alkylpiperidine compound (À)-acanthocyclamine A (1) has been obtained from the methanolic extract of Acanthostrongylophora ingens (order Haplosclerida, family Petrosiidae) collected from Wakatobi Marine National Park in South East Sulawesi, Indonesia. The structure of 1 was investigated by extensive 1D-and 2D-NMR experiments. The absolute configuration of 1 was established by X-ray crystallography from anomalous dispersion effects using Cu radiation as C2 (R), C3 (R), C7 (R), and C9 (R). A plausible biosynthetic scheme leading to 1 is presented, and compared with the biosynthetic pathway proposed for the manzamine alkaloids.
New cytotoxic acridine alkaloids from two deep water marine sponges of the family
Tetrahedron Letters, 1989
Fused ring alkaloids having the pyrido[4,3,2-mnlacridine skeleton comprise a new class of marine natural products.laeh Their biological activityle and challenging structure elucidation make them an interesting group of cumpoundr. In this paper we report the identification of four new cytotoxic and structaraUy related alkaloid. nordercitin (I), dercitamine {2), dercitamide (3), and cyclodercitin (4). The extracts of two sponges, a deep violet Dercitus sp. and a red Stelletta sp., collected by manned submersible at depths of 152m and 70m respectively, in the Bahamas,2 inhibited growth of murine P388 leukemia cells when screened on shipboard at the site of collection. The organisms were kept frozen until extraction with MeOH:toluene (3:l) and 100% MeOH. Fractionation of the Dercitus extract by centrifugal countercurrent chromatography using MeOH:CH$12:Hz0(5:5:3) gave the previously described dercitin (5) as the major antitumor alkaloid.te Further purification of the fractions containing minor metabolites by HPLC (NH, stationary phase, solvent system-CHsCN: MeOH: CHzC12(4:4:1) containing 1% NH,OH) gave cyclodercitin (4), and two N-oxides of dercitin(N-1 and N-15). Using similar chromatographic procedures, the extract from Stetleta sp. gave nordercitin (1). dercitamine (Z), and dercitamide (3). The pyrido[4,3,2-mn]thiazolo[3,2-b]acridinium-9-ethyl skeleton (Figure 1) in each compound was suggested by the characteristic UV absorption pattern, (&,, (MeOH) 245 (t 13,800), 307 (t l&900), and 361 nm (t 39OO)), which was highly sensitive to the pH of the medium. Further, the aromatic region of the 'H nmr spectra of each compound consisted of seven signals: a downfield one proton singlet for the thiazole proton (H-l I), two vicinal olefin proton signals (H-2 and H-3) and signals for four protons on an ortho disubstituted aromatic ring (H-4-H-7). In the aliphatic region signals for two vicinal methylene groups were observed. Three bond CH connectivities for all the carbons except for C-12c could be observed in spectra from COLOC3 and HMB@ experiments (Table 1). Comparison of the 'H and t3C spectra (Tables I & 2) of the four compounds showed that they differed from dercitin (5) in the substituents on N-l and/or on the ethyl side chain. The presence of a methyl function on N-l in 4-6 could be readily detected by a 3 proton singlet observed at 3.5 to 3.9 ppm in CD,OD or between 4 to 5.6 ppm in TPA-d and a corresponding carbon signal observed between 44 to 52 ppm in either solvent. The N-l methyl protons also showed 3-bond connectivity to C-2 and C-12b. Further, the presence of a methyl group on N-l could be deduced from the color of the compound in solution: both types turn deep red to violet(480-510 nm) in acidic medium, but the N-methylated compounds turn blue (590 nm) in basic medium while the others turn yellow (430nm). 9,10-dihydro-l-methylpyrido[4,3,2-mn]pyrrolo[3,2,1-de]thiazolo[5,4-b] acridinium ion, to cyclodercitin (4) and the correct numbering of this ring system is shown in Figure 2,6. All compounds inhibited proliferation of P388 murine leukemia cells in vitro and compounds 1, 2, and 3 exhibited immunosuppressant activity.7 The organisms were collected using HBOI Johnson-Sea-Link submersibles and voucher specimens are deposited in the Indian River Coastal Zone Museum (IRCZM).
Marine drugs, 2016
Two new cyclotetrapeptides, sartoryglabramides A (5) and B (6), and a new analog of fellutanine A (8) were isolated, together with six known compounds including ergosta-4, 6, 8 (14), 22-tetraen-3-one, ergosterol 5, 8-endoperoxide, helvolic acid, aszonalenin (1), (3R)-3-(1H-indol-3-ylmethyl)-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione (2), takakiamide (3), (11aR)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione (4), and fellutanine A (7), from the ethyl acetate extract of the culture of the marine sponge-associated fungus Neosartorya glabra KUFA 0702. The structures of the new compounds were established based on extensive 1D and 2D spectral analysis. X-ray analysis was also used to confirm the relative configuration of the amino acid constituents of sartoryglabramide A (5), and the absolute stereochemistry of the amino acid constituents of sartoryglabramide A (5) and sartoryglabramides B (6) was determined by chiral HPLC analysis of their hydrolysates by co-injec...
Journal of Natural Products, 2007
Bioassay-guided fractionation of Papua New Guinea collections of Leucosolenia sp. resulted in the isolation of the novel compounds leucosolenamines A (5) and B (6) and the known compound thymidine (7). Compound 5 contains a 2-aminoimidazole core substituted at C-4 and C-5 by an N,N-dimethyl-5,6-diaminopyrimidine-2,4-dione and a benzyl group, respectively. Compound 6 retains the same core structure; however C-4 is substituted by a 5,6-diamino-1,3-dimethyl-4-(methylimino)-3,4-dihydropyrimidin-2(1H)-one moiety. This substitution pattern is unique and has never been observed in calcareous imidazole alkaloid chemistry. Leucosolenamine A (5) was mildly cytotoxic against the murine colon adenocarcinoma C-38 cell line. The sustained position of marine sponges as a source of structurally diverse and biologically active natural products was emphasized in a recent review article covering the 2003 literature. 1 Complex sponge natural products have also been the basis for the development of several clinical leads. 2 At the top of the list are natural products containing multiple chiral centers such as the bengamides, 3 fijianolides, 4 the halichondrin analogue E7389, 5 and the discodermolides 6 or sponge metabolites with exotic functionality, as in the psammaplins. 7 The research described in this paper began with the goal of adding additional unique structures to the rapidly growing list of sponge-derived alkaloids. In this regard, the Calcarea class of sponges is now recognized as a reliable source of richly bioactive metabolites possessing a 2-aminoimidazole 8 core that is often further substituted at the C-4 and C-5 positions. 9 The range of substitution patterns observed to date at these positions include (a) benzyl side chains, (b) oxo groups at C-4, and (c) annulation by five-or six-membered rings.
Marine Drugs
A chemical study of the CH2Cl2−MeOH (1:1) extract from the sponge Ernsta naturalis collected in Rodrigues (Mauritius) based on a molecular networking dereplication strategy highlighted one novel aminopyrimidone alkaloid compound, ernstine A (1), seven new aminoimidazole alkaloid compounds, phorbatopsins D–E (2, 3), calcaridine C (4), naamines H–I (5, 7), naamidines J–K (6, 8), along with the known thymidine (9). Their structures were established by spectroscopic analysis (1D and 2D NMR spectra and HRESIMS data). To improve the investigation of this unstudied calcareous marine sponge, a metabolomic study by molecular networking was conducted. The isolated molecules are distributed in two clusters of interest. Naamine and naamidine derivatives are grouped together with ernstine in the first cluster of twenty-three molecules. Phorbatopsin derivatives and calcaridine C are grouped together in a cluster of twenty-one molecules. Interpretation of the MS/MS spectra of other compounds of th...
Novel Natural Product Discovery from Marine Sponges and their Obligate Symbiotic Organisms
Discovery of novel natural products is an accepted method for the elucidation of pharmacologically active molecules and drug leads. Best known sources for such discovery have been terrestrial plants and microbes, accounting for about 85% of the approved natural products in pharmaceutical use (1), and about 60% of approved pharmaceuticals and new drug applications annually (2). Discovery in the marine environment has lagged due to the difficulty of exploration in this ecological niche. Exploration began in earnest in the 1950's, after technological advances such as scuba diving allowed collection of marine organisms, primarily at a depth to about 15m.