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Journal of the American Chemical Society Apr 2010The first organocatalytic enantioselective radical polycyclization has been accomplished using singly occupied molecular orbital (SOMO) catalysis. The presented strategy...
The first organocatalytic enantioselective radical polycyclization has been accomplished using singly occupied molecular orbital (SOMO) catalysis. The presented strategy relies on a selective single-electron oxidation of chiral enamines formed by condensation of polyenals with an imidazolidinone catalyst employing a suitable copper(II) oxidant. The reaction proceeds under mildly acidic conditions at room temperature and shows compatibility with an array of electron-poor as well as electron-rich functional groups. Upon termination by radical arylation followed by subsequent oxidation and rearomatization, a range of polycyclic aldehydes were accessed (12 examples, 54-77% yield, 85-93% ee). The enantioselective formation of up to six new carbocycles in a single catalyst-controlled cascade is described. Evidence for a radical-based cascade mechanism is indicated by a series of experimental results.
Topics: Aldehydes; Catalysis; Cyclization; Imidazolidines; Molecular Structure; Polyenes; Stereoisomerism
PubMed: 20334384
DOI: 10.1021/ja100185p -
Applied and Environmental Microbiology Oct 2011Polyene macrolides are important antibiotics used to treat fungal infections in humans. In this work, acyltransferase (AT) domain swaps, mutagenesis, and...
Initiation of polyene macrolide biosynthesis: interplay between polyketide synthase domains and modules as revealed via domain swapping, mutagenesis, and heterologous complementation.
Polyene macrolides are important antibiotics used to treat fungal infections in humans. In this work, acyltransferase (AT) domain swaps, mutagenesis, and cross-complementation with heterologous polyketide synthase domain (PKS) loading modules were performed in order to facilitate production of new analogues of the polyene macrolide nystatin. Replacement of AT(0) in the nystatin PKS loading module NysA with the propionate-specific AT(1) from the nystatin PKS NysB, construction of hybrids between NysA and the loading module of rimocidin PKS RimA, and stepwise exchange of specific amino acids in the AT(0) domain by site-directed mutagenesis were accomplished. However, none of the NysA mutants constructed was able to initiate production of new nystatin analogues. Nevertheless, many NysA mutants and hybrids were functional, providing for different levels of nystatin biosynthesis. An interplay between certain residues in AT(0) and an active site residue in the ketosynthase (KS)-like domain of NysA in initiation of nystatin biosynthesis was revealed. Some hybrids between the NysA and RimA loading modules carrying the NysA AT(0) domain were able to prime rimocidin PKS with both acetate and butyrate units upon complementation of a rimA-deficient mutant of the rimocidin/CE-108 producer Streptomyces diastaticus. Expression of the PimS0 loading module from the pimaricin producer in the same host, however, resulted in production of CE-108 only. Taken together, these data indicate relaxed substrate specificity of NysA AT(0) domain, which is counteracted by a strict specificity of the first extender module KS domain in the nystatin PKS of Streptomyces noursei.
Topics: Acetyltransferases; Anti-Infective Agents; Chromatography, High Pressure Liquid; Genetic Complementation Test; Humans; Macrolides; Metabolic Networks and Pathways; Models, Molecular; Molecular Structure; Mutagenesis; Mutant Proteins; Polyenes; Polyketide Synthases; Recombinant Fusion Proteins; Recombination, Genetic; Streptomyces
PubMed: 21821762
DOI: 10.1128/AEM.05781-11 -
Molecules (Basel, Switzerland) Feb 2021Three new polyene compounds, talacyanols A-C (-), along with two known compounds, ramulosin () and eurothiocin A (), were isolated from the marine fungus derived from a...
Three new polyene compounds, talacyanols A-C (-), along with two known compounds, ramulosin () and eurothiocin A (), were isolated from the marine fungus derived from a seaweed sp. Structures of - were established by one-dimensional and two-dimensional (1D/2D) NMR, HR-ESIMS, and the modified Mosher's methods, as well as comparison with previously reported literature data. All the compounds (-) were tested for their in vitro cytotoxic and anti-neuroinflammatory activities. Among them, showed moderate cytotoxic activity against a panel of cancer cell lines (HCT-15, NUGC-3, NCI-H23, ACHN, PC-3, and MDA-MB-231) with GI values ranging from 44.4 to 91.6 μM, whereas compounds and exhibited anti-neuroinflammatory effect without cytotoxicity against all the tested cell lines.
Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Humans; Inflammation; Polyenes; Talaromyces
PubMed: 33562648
DOI: 10.3390/molecules26040836 -
Bioorganic & Medicinal Chemistry Letters Sep 2022Ambreinolide is a natural terpenoid with great value for perfume industry and natural product synthesis. Herein we report a novel total synthesis of ambreinolide on...
Ambreinolide is a natural terpenoid with great value for perfume industry and natural product synthesis. Herein we report a novel total synthesis of ambreinolide on multigram-scale that employs a regio- and diastereoselective, high yielding, proton-initiated polyene cyclization using a catalyst easily generated in situ. Molecular structures were unambiguously confirmed by X-ray crystallography.
Topics: Crystallography, X-Ray; Cyclization; Molecular Structure; Polyenes; Stereoisomerism; Terpenes
PubMed: 35700954
DOI: 10.1016/j.bmcl.2022.128845 -
The Journal of Antibiotics Aug 1982The three polyene macrolide antibiotics, fungichromin, lagosin, and cogomycin, previously described as having some stereochemical differences at one or more centers, are... (Comparative Study)
Comparative Study
The three polyene macrolide antibiotics, fungichromin, lagosin, and cogomycin, previously described as having some stereochemical differences at one or more centers, are shown by countercurrent distribution, high-performance liquid chromatography, carbon-13 nuclear magnetic resonance spectroscopy, circular dichroism, and biological studies to be identical in all respects, including stereochemical aspects. The differences observed earlier in their properties have now been ascribed to varying amounts of impurities, which are separable by high-performance liquid chromatography. All three antibiotics contain one major and several minor components.
Topics: Antibiotics, Antineoplastic; Antifungal Agents; Chromatography, High Pressure Liquid; Macrolides; Magnetic Resonance Spectroscopy; Polyenes
PubMed: 7142017
DOI: 10.7164/antibiotics.35.988 -
Biomaterials Nov 2018Intra-articular injection of hyaluronic acid (HA) is used to treat osteoarthritis (OA) as a viscosupplement, yet it only provides short-term benefit because HA is...
Intra-articular injection of hyaluronic acid (HA) is used to treat osteoarthritis (OA) as a viscosupplement, yet it only provides short-term benefit because HA is cleaved by hyaluronidase and cleared out of the joint after several days. Therefore, we developed a new polymer biolubricant based on poly-oxanorbornane carboxylate to enhance joint lubrication for a prolonged time. Rheological and biotribological studies of the biolubricant reveal viscoelastic properties and coefficient of friction equivalent and superior to that of healthy synovial fluid, respectively. Furthermore, in an ex vivo bovine cartilage plug model, the biolubricant exhibits superior long-term reduction of friction and wear prevention compared to saline and healthy synovial fluid. ISO 10993 biocompatibility tests demonstrate that the biolubricant polymer is non-toxic. In an in vivo rat medial meniscal tear OA model, where the performance of the leading HA viscosupplement (Synvisc-one) is comparable to the saline control, treatment with the biolubricant affords significant chondroprotection compared to the saline control.
Topics: Animals; Biomechanical Phenomena; Cell Line; Chondrocytes; Furans; Humans; Injections, Intra-Articular; Knee Injuries; Knee Joint; Male; Meniscus; Mice; NIH 3T3 Cells; Osteoarthritis; Polyenes; Rats, Inbred Lew; Synovial Fluid; Viscosupplements
PubMed: 30099277
DOI: 10.1016/j.biomaterials.2018.08.009 -
Dental Materials Journal Jun 2024There is a growing need for a mouthguard sheet material with higher shock absorption and dispersion capacity than those obtained by conventional materials. A five-layer...
There is a growing need for a mouthguard sheet material with higher shock absorption and dispersion capacity than those obtained by conventional materials. A five-layer mouthguard sheet material was previously developed using laminated ethylene vinyl acetate and polyolefin copolymer resin. In this study, the shock absorption capacity and dispersion capability of the new sheet material were investigated and compared with those of other materials. Impact testing for the new sheet material showed that the force required to displace the sheet by 1 mm was significantly higher at all thicknesses (p<0.001), whereas the puncture energy and displacement were significantly lower than those for ethylene vinyl acetate (p<0.05). The five-layer mouthguard sheet material successfully absorbed and resisted shock. Therefore, the sheet material potentially increases resistance to applied deformation in teeth and alveolar bone and maintains structure. The five-layer sheet material could expand the range of mouthguard products and help prevent oral trauma.
Topics: Mouth Protectors; Materials Testing; Polyenes; Vinyl Compounds; Equipment Design; Polyvinyls; Stress, Mechanical; Dental Stress Analysis
PubMed: 38583997
DOI: 10.4012/dmj.2023-179 -
PloS One 2014A novel xanthomonadin-dialkylresorcinol hybrid named arcuflavin was identified in Azoarcus sp. BH72 by a combination of feeding experiments, HPLC-MS and MALDI-MS and...
A novel xanthomonadin-dialkylresorcinol hybrid named arcuflavin was identified in Azoarcus sp. BH72 by a combination of feeding experiments, HPLC-MS and MALDI-MS and gene clusters encoding the biosynthesis of this non-isoprenoid aryl-polyene containing pigment are reported. A chorismate-utilizing enzyme from the XanB2-type producing 3- and 4-hydroxybenzoic acid and an AMP-ligase encoded by these gene clusters were characterized, that might perform the first two steps of the polyene biosynthesis. Furthermore, a detailed analysis of the already known or novel biosynthesis gene clusters involved in the biosynthesis of polyene containing pigments like arcuflavin, flexirubin and xanthomonadin revealed the presence of similar gene clusters in a wide range of bacterial taxa, suggesting that polyene and polyene-dialkylresorcinol pigments are more widespread than previously realized.
Topics: Anisoles; Azoarcus; Biological Products; Gas Chromatography-Mass Spectrometry; Gene Order; Genome, Bacterial; Molecular Structure; Multigene Family; Pigments, Biological; Polyenes; Reproducibility of Results; Resorcinols; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 24618669
DOI: 10.1371/journal.pone.0090922 -
Biointerphases Nov 2018Antimicrobial surface coatings that act through a contact-killing mechanism (not diffusive release) could offer many advantages to the design of medical device coatings...
Antimicrobial surface coatings that act through a contact-killing mechanism (not diffusive release) could offer many advantages to the design of medical device coatings that prevent microbial colonization and infections. However, as the authors show here, to prevent arriving at an incorrect conclusion about their mechanism of action, it is essential to employ thorough washing protocols validated by surface analytical data. Antimicrobial surface coatings were fabricated by covalently attaching polyene antifungal drugs to surface coatings. Thorough washing (often considered to be sufficient to remove noncovalently attached molecules) was used after immobilization and produced samples that showed a strong antifungal effect, with a log 6 reduction in colony forming units. However, when an additional washing step using surfactants and warmed solutions was used, more firmly adsorbed compounds were eluted from the surface as evidenced by XPS and ToF-SIMS, resulting in reduction and complete elimination of antifungal activity. Thus, polyene molecules covalently attached to surfaces appear not to have a contact-killing effect, probably because they fail to reach their membrane target. Without additional stringent washing and surface analysis, the initial favorable antimicrobial testing results could have been misinterpreted as evidencing activity of covalently grafted polyenes, while in reality activity arose from desorbing physisorbed molecules. To avoid unintentional confirmation bias, they suggest that binding and washing protocols be analytically verified by qualitative/quantitative instrumental methods, rather than relying on false assumptions of the rigors of washing/soaking protocols.
Topics: Antifungal Agents; Candida albicans; Coated Materials, Biocompatible; Colony Count, Microbial; Photoelectron Spectroscopy; Polyenes; Spectrometry, Mass, Secondary Ion; Surface Properties
PubMed: 30482023
DOI: 10.1116/1.5050043 -
Marinisporolides, polyene-polyol macrolides from a marine actinomycete of the new genus Marinispora.The Journal of Organic Chemistry Jan 2009Two new polyene macrolides, marinisporolides A and B (1, 2), were isolated from the saline culture of the marine actinomycete, strain CNQ-140, identified as a member of...
Two new polyene macrolides, marinisporolides A and B (1, 2), were isolated from the saline culture of the marine actinomycete, strain CNQ-140, identified as a member of the new marine genus Marinispora. The marinisporolides are 34-membered macrolides composed of a conjugated pentaene and several pairs of 1,3-dihydroxyl functionalities. Marinisporolide A (1) contains a bicyclic spiro-bis-tetrahydropyran ketal functionality, while marinisporolide B (2) is the corresponding hemiketal. The structures of these new compounds were assigned by combined spectral and chemical methods including extensive 2D NMR experiments and correlations of (13)C NMR data with Kishi's Universal NMR Database. Chemical modifications, including methanolysis, acetonide formation, and application of the modified Mosher method, provided the full stereostructures of these molecules. Three additional macrolides, marinisporolides C-E (3-5), which are olefin geometric isomers of marinisporolide A (1), were also isolated and their structures defined. Under room light, marinisporolides A and B readily photoisomerize to C-E indicating that they are most likely produced by photochemical conversion during the cultivation or isolation procedures. Although polyenes, marinisporolides A (1) and B (2) showed weak to no antifungal activity against Candida albicans.
Topics: Actinobacteria; Alkenes; Isomerism; Macrolides; Magnetic Resonance Spectroscopy; Polyenes; Polymers
PubMed: 19132943
DOI: 10.1021/jo801944d