Coibacins A–D, Antileishmanial Marine Cyanobacterial Polyketides with Intriguing Biosynthetic Origins (original) (raw)
Related papers
2001
Chapter II: K. Shawn Watts acquired x-ray diffraction data and solved the crystal structure of hectochiorin. Drs. Pascal Verclier-Pinard and Ernest Hamel conducted the studies on the stimulation of actin polymerization. Chapter III: Dr. R. Thomas Williamson acquired the ACCORD-ADEQAUTE and the 1H-'5N HMBC data for jamaicamide A. Lisa Nogle assisted in the feeding, isolation, and acquisition of 13C NMR data for the biosynthesis studies ofjamaicamide A. In addition she completed the isolation and structure elucidation ofjamaicamide C. Chapter IV: Dr. Namthip Sitachitta performed the experiments that are noted as "Review of previous feeding studies" in the chapter. The laboratory of Dr. Christine L. Willis at the University of Bristol provided all chirally labeled substrates for the biosynthetic feeding experiments.
Chemistry & Biology, 2004
While the biological activities reported for marine cyanobacterial metabolites vary widely, three major trends emerge. A number of these metabolites target either the polymerization of tubulin (e.g., dolastatin 10 [4], curacin A [5]) or the polymerization of actin (e.g., hectochlorin [6], majusculamide C [7]). Additionally, a growing number of potently bioactive metabolites from cyanobacteria Corvallis, Oregon 97331 target the mammalian voltage-gated sodium channel, either as blockers (kalkitoxin [8]) or activators (antillatoxin [9]). Hence, we have employed a simple cell-based Summary screen of marine cyanobacterial extracts and compounds for detecting new neurotoxins that modulate A screening program for bioactive compounds from marine cyanobacteria led to the isolation of jamai-the activity of this important ion channel [10]. This approach has been fruitful, and we report here the results camides A-C. Jamaicamide A is a novel and highly functionalized lipopeptide containing an alkynyl bro-that followed from initial detection of neurotoxic activity in a Jamaican collection of Lyngbya majuscula. Because mide, vinyl chloride, -methoxy eneone system, and pyrrolinone ring. The jamaicamides show sodium of the unusual structures of the isolated compounds, jamaicamides A-C ), we have been motivated channelblocking activity and fish toxicity. Precursor feeding to jamaicamide-producing cultures mapped to examine their biosynthetic origins in considerable detail. Isotope-labeling experiments with producing lab-out the series of acetate and amino acid residues and helped develop an effective cloning strategy for the oratory cultures identified the component building blocks, whereas their assembly has been partially eluci-biosynthetic gene cluster. The 58 kbp gene cluster is composed of 17 open reading frames that show an dated by a molecular genetics approach. In this work, we report the discovery, structure elucidation, biological exact colinearity with their expected utilization. A novel cassette of genes appears to form a pendent properties, biosynthetic subunits, and sequence of the gene cluster encoding for the biosynthesis of jamai-carbon atom possessing the vinyl chloride functionality; at its core this contains an HMG-CoA synthase-camides A-C. like motif, giving insight into the mechanism by which this functional group is created.
Stereopermutation on the Putative Structure of the Marine Natural Product Mucosin
Molecules
A stereodivergent total synthesis has been executed based on the plausibly misassigned structure of the unusual marine hydrindane mucosin (1). The topological connectivity of the four contiguous all-carbon stereocenters has been examined by selective permutation on the highlighted core. Thus, capitalizing on an unprecedented stereofacial preference of the cis-fused bicycle[4.3.0]non-3-ene system when a Michael acceptor motif is incorporated, copper-mediated conjugate addition furnished a single diastereomer. Cued by the relative relationship reported for the appendices in the natural product, the resulting anti-adduct was elaborated into a probative target structure 1*.
The Journal of Organic Chemistry, 1992
of inhibition (mm) vs log, concn (pg/mL). Purification of Capreomycins IA and IB. The fermentation (200 mL) was incubated at 30 "C, 250 rpm for 6 days, the culture then filtered through Celite, and the filter cake washed with water. Activated charcoal (9.0 g) was added to the combined filtrate and washings and the mixture allowed. Activated charcoal (9.0 g) was added to the combined filtrate and washings and the mixture allowed to stand for ca. 30 min. The mixture was filtered through Celite and the fdtrate discarded. Successive washings of the filter cake with water (60 mL) and 0.05 M HC1 (60 mL) were also discarded. The filter cake was then eluted with acidic aqueous acetone (200 mL of acetone and 4.25 mL of concd HC1 per L of deionized water) in a period of 15 min. The acetone eluate was concentrated in vacuo to a small volume (ca. 8 mL) and then transferred, with stirring, to acetone (10 times the volume of the concentrate) and the mixture allowed to stand in a cold room (4 "C) overnight. The acetone was decanted, and the resulting reddish-brown oily precipitate was dissolved in 6 M HCl(3 mL). This was fiitered into stirred MeOH (36 mL), and the precipitate was then collected. A column of Amberlite CG-50 (100-200 mesh, NH4+) (1.0 X 42.5 cm) was allowed to equilibrate in 0.4 M NH40Ac, buffered to pH 9.0, at 4 ' C. The sample (typically 450 mg) was applied to the column in a small volume (ca. 3 mL) of the buffer. The resin was eluted first with a gradient from 0.4 to 0.8 M NH40Ac (225 mL each) and then isocratically with 0.8 M NH40Ac (300 mL). Fractions (ca. 5 mL) were collected at 25-min intervals and were monitored by UV (280 and 254 nm). On the basis of the UV profile, fractions containing either IA or IB were combined and concentrated on a rotary evaporator to a small volume. Capreomycin IB typically began to appear in fraction 20 and IA typically began to appear in fraction 34. The concentrates were desalted separately with a column (3.0 X 10.5 cm) of Sephadex G-10 eluted with water. Capreomycin I A mp 244-248 ' C dec (lit? mp 246-248 ' C dec), [(Y]~-19.6' (lit? ["ID-21.9'). Capreomycin IB: mp 256-259 ' C dec (lit? mp 253-255 "C dec), [(YID Incorporation of [2,3,3,5,5-2H~]Ardnine, 8a. A mixture of 8a.HC13, (60.1 mg, 279 pmol, 195% 2H at each position) and ~~-[l-'~C]arginine (11.42 pCi) in water (10 mL) was fed in three-43.6' (lit.B [(Y]D-44.6'). equal portions to a 200-mL production culture 12,32, and 56 h after inoculation with a seed culture. After 6 days the fermentation was worked up, and bioassay indicated 972 mg of total capreomycins. The MeOH precipitate (394 mg) was chromatographed on a CG-50 column (1.5 X 46 cm), eluting as described above; 8.5 mL fractions were taken. The combined IB (2a) fractions were desalted on a Sephadex G-10 column (4.6 X 10.5 cm), and center fractions containing pure 2a were lyophilized and combined to give 56 mg. A portion of this (31.1 mg) was dissolved in deuterium-depleted water, lyophilized, and dissolved in an additional aliquot of the same solvent (0.5 mL). t-BuOH (25 pL) was added for chemical shift reference and deuterium quantitation. A standmd % NMR spectrum (61.4 MHz) was first obtained at room temperature with sweep width 1645 Hz, 4 K data points zero-filled to 8 K, 9 0 ' pulse width, 1.245s acquisition time, 48 287 scans. A second spectrum was obtained using the Bruker routine WATER-AUR, an inversion recovery water suppression sequence [Pl 90°, P2 240°, D10.05 8, D2 0.2 s (to approximate T1 of HOD), acquisition time 0.6226 a] with 102200 scans accumulated: S 1.28 (t-BuOH), 3.33 (H-5), 4.44 (H-3), and 4.92 (residual HOD). A third spectrum was obtained using the inversion recovery sequence at 330 K 8 1.28,3.34 (H-5), 4.42 (H-3), 4.51 (residual HOD inverted). The combined IA (la) fractions were similarly desalted, and center fractions containing pure la were lyophilized and combined to give 54 mg, which was similarly analyzed by ,H NMR.
Lindgomycin, an Unusual Antibiotic Polyketide from a Marine Fungus of the Lindgomycetaceae
Marine drugs, 2015
An unusual polyketide with a new carbon skeleton, lindgomycin (1), and the recently described ascosetin (2) were extracted from mycelia and culture broth of different Lindgomycetaceae strains, which were isolated from a sponge of the Kiel Fjord in the Baltic Sea (Germany) and from the Antarctic. Their structures were established by spectroscopic means. In the new polyketide, two distinct domains, a bicyclic hydrocarbon and a tetramic acid, are connected by a bridging carbonyl. The tetramic acid substructure of compound 1 was proved to possess a unique 5-benzylpyrrolidine-2,4-dione unit. The combination of 5-benzylpyrrolidine-2,4-dione of compound 1 in its tetramic acid half and 3-methylbut-3-enoic acid pendant in its decalin half allow the assignment of a new carbon skeleton. The new compound 1 and ascosetin showed antibiotic activities with IC50 value of 5.1 (±0.2) µM and 3.2 (±0.4) μM, respectively, against methicillin-resistant Staphylococcus aureus.
Natural product biosynthesis in bacteria associated with marine organisms
Records of Pharmaceutical and Biomedical Sciences
Because antibiotics are becoming less effective and there is an increase in the number of cases of cancer, it is critical that researchers continue their search for novel natural antimicrobials and anti-cancer medicines. Screening marine organisms for the purpose of developing new medications is still in its infant stages especially from nudibranchs. Many Polyketides, non-ribosomal peptides, terpenes, and post-ribosomal peptides are synthesized by marine organisms' symbiotic bacteria. In this review, we summarized the sum of the previous works done on bacteria associated with marine organisms for identifying bioactive metabolites. We discussed whether the host is responsible for the production of these metabolites or its symbiotic bacteria. Also, factors that may affect the abundance of symbiotic bacteria and bioactive compounds such as different habitats and environmental circumstances like food and location have been shown and discussed. We also discussed why nudibranchs deserve more studies for mining secondary metabolites in their symbiotic bacteria.
Compounds from macro marine organisms are presumed to owe their biosynthetic origins to associated microbial symbionts, although few definitive examples exist. An upsurge in the recent literature from 2012 to 2013 has shown that four compounds previously reported from macro marine organisms are in fact biosynthesized by non-photosynthetic Gram-negative bacteria (NPGNB). Structural parallels between compounds isolated from macro marine organisms and NPGNB producers form the basis of this review. Although less attention has been given to investigating the chemistry of NPGNB sources, there exists a significant list of structural parallels between NPGNB and macro marine organism derived compounds. Alternatively, of the thousands of compounds isolated from Gram-positive actinomycetes, few structural parallels with macro marine organisms are known. A summary of small molecules isolated from marine NPGNB sources is presented, including compounds isolated from marine myxobacteria. From this assemblage of structural parallels and diverse chemical structures, it is hypothesized that the potential for the discovery of inspirational molecules from NPGNB sources is vast and that the recent spike in the literature of macro marine compounds owing their biosynthetic origin to NPGNB producers represents a turning point in the field.
Recent Synthesis of Marine Natural Products with Antibacterial Activities
Anti-Infective Agents in Medicinal Chemistry, 2007
The emergence of multiple-drug-resistant strains of bacteria, the indiscriminate use of antibiotics and the increasing susceptibility of individuals with acquired immunodeficiency syndrome (AIDS) to infection from Mycobacterium induce an urgent need for development of new strategies to treat bacterial infections. Many natural products from marine sources are endowed with promising antibacterial activities, thus representing invaluable leads in the plans for antibiotic drug discovery. In this context, organic synthesis plays a decisive role in confirming (or revising) the chemical structures of the natural compounds allowing also access to suitable amounts of the target (and its analogs) for structureactivity relationship (SAR) investigations. In this overview, we focus on the total and partial synthesis of antibacterial marine metabolites and their related compounds published since 2000, discussing the retrosynthetic analysis of the strategies adopted. It includes the total synthesis of pestalone, squalamine, abyssomicin C and litosterol, the revised structure by total synthesis for the antituberculosis pseudopteroxazole and agelasine C, the preparation of the core-structure of zamamistatin and access to momeric and dimeric congeners of active peptide halocidin. Review with 132 references.