- The Botrytis cinerea type III polyketide synthase shows unprecedented high catalytic efficiency toward long chain acyl-CoAs
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BPKS from Botrytis cinerea is a novel type III polyketide synthase that accepts C4-C18 aliphatic acyl-CoAs and benzoyl-CoA as the starters to form pyrones, resorcylic acids and resorcinols through sequential condensation with malonyl-CoA. The catalytic efficiency (kcat/K m) of BPKS was 2.8 × 105 s-1 M -1 for palmitoyl-CoA, the highest ever reported. Substrate docking analyses addressed the unique features of BPKS such as its high activity and high specificity toward long chain acyl-CoAs.
- Jeya, Marimuthu,Kim, Tae-Su,Tiwari, Manish Kumar,Li, Jinglin,Lee, Jung-Kul,Zhao, Huimin
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Read Online
- Nonpeptidic potent HIV-1 protease inhibitors: (4-hydroxy-6-phenyl-2-oxo- 2H-pyran-3-yl)thiomethanes that span P1-P2' subsites in a unique mode of active site binding
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Using molecular modeling and the information derived from the X-ray crystal structure of HIV-1 protease (HIV PR) complexed with the pyran-2-one l, a series of (4-hydroxy-6-phenyl-2-oxo-2H-pyran-3-yl)thiomethanes was designed and analyzed as novel, nonpept
- Prasad,Para,Tummino,Ferguson,McQuade,Lunney,Rapundalo,Batley,Hingorani,Domagala,Gracheck,Bhat,Liu,Baldwin,Erickson,Sawyer
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Read Online
- Synthesis and antimicrobial activity of new prenylated 2-pyrone derivatives
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A series of new monoprenylated and diprenylated 2-pyrone derivatives with different halogen substituents were synthesized from the corresponding 6-aryl-4-hydroxy-2-pyrones by prenylation reactions. The compounds were evaluated for antibacterial activity and displayed significant in vitro activity with the highest activity shown by the monoprenylated 6-aryl-2-pyrones. All the compounds except the bromine-containing analogs were active against one or more tested bacteria, with Escherichia coli being the most susceptible of the test organisms. With the remarkable antibacterial activity of eight of the compounds against a drug-resistant β-lactamase-producing Klebsiella pneumoniae, a synergistic evaluation between each of these compounds and ampicillin was undertaken. Out of the eight combinations studied, synergistic effects were observed with two compounds, 4-(3-methylbut-2-enoxy)-6-phenyl-2H-pyran-2-one and 6-(4-fluorophenyl)-4-(3-methylbut-2-enoxy)-2H-pyran-2-one. Both compounds, at half the individual MIC values, were able to lower the MIC of ampicillin in combinations from 2500 to 2.4 μg/mL (1/1041 of MIC).
- Chukwujekwu, Jude C.,Obi, Grace,van Heerden, Fanie R.
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- NEW ANTIBACTERIAL COMPOUNDS
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The present invention relates to novel antibacterial compounds, pharmaceutical compositions containing them and their use as antimicrobials.
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Page/Page column 43-44
(2016/07/05)
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- Gold- or Silver-Catalyzed Syntheses of Pyrones and Pyridine Derivatives: Mechanistic and Synthetic Aspects
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3-Oxo-5-alkynoic acid esters, on treatment with a carbophilic catalyst, undergo 6-endo-dig cyclization reactions to furnish either 2-pyrones or 4-pyrones in high yields. The regiochemical course can be dialed in by the proper choice of the alcohol part of the ester and the π-acid. This transformation is compatible with a variety of acid-sensitive groups as witnessed by a number of exigent applications to the total synthesis of natural products, including pseudopyronine A, hispidine, phellinin A, the radininol family, neurymenolide, violapyrone, wailupemycin and an unnamed brominated 4-pyrone of marine origin. Although the reaction proceeds well in neutral medium, the rate is largely increased when HOAc is used as solvent or co-solvent, which is thought to favor the protodeauration of the reactive alkenyl-gold intermediates as the likely rate-determining step of the catalytic cycle. Such intermediates are prone to undergo diauration as an off-cycle event that sequesters the catalyst; this notion is consistent with literature data and supported by the isolation of the gem-diaurated complexes 12 and 15. Furthermore, silver catalysis allowed access to be gained to 2-alkoxypyridine and 2-alkoxyisoquinoline derivatives starting from readily available imidate precursors.
- Preindl, Johannes,Jouvin, Kvin,Laurich, Daniel,Seidel, Günter,Fürstner, Alois
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supporting information
p. 237 - 247
(2016/01/25)
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- Pd-catalysed intramolecular regioselective arylation of 2-pyrones, pyridones, coumarins and quinolones by C–H bond functionalization
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The intramolecular arylation of 2-pyrones, 2-pyridones, coumarins and quinolones is reported using PdII precatalyst sources without added phosphine ligands. The excellent yields and convenient reagents enables the formation of various analogues
- Nolan, Marie-Therese,Bray, Joshua T.W.,Eccles, Kevin,Cheung, Man Sing,Lin, Zhenyang,Lawrence, Simon E.,Whitwood, Adrian C.,Fairlamb, Ian J.S.,McGlacken, Gerard P.
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p. 7120 - 7127
(2017/09/12)
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- Cloning and structure-function analyses of quinolone- and acridone-producing novel type III polyketide synthases from citrus microcarpa
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Background:Type III polyketide synthases (PKSs) synthesize various polyketide and alkaloid scaffolds. Results:QNS synthesizes quinolone as the single product, whereas ACS produces acridone as the major product. Conclusion:QNS and ACS are novel quinolone- and acridone-producing type III PKSs, respectively. Significance:Structure-function analyses of QNS and ACS provide insights into molecular bases for alkaloid biosyntheses.
- Mori, Takahiro,Shimokawa, Yoshihiko,Matsui, Takashi,Kinjo, Keishi,Kato, Ryohei,Noguchi, Hiroshi,Sugio, Shigetoshi,Morita, Hiroyuki,Abe, Ikuro
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p. 28845 - 28858
(2013/10/22)
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- Total synthesis of neurymenolide-A Based on a gold-catalyzed synthesis of 4-hydroxy-2-pyrones
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Treat me gently: For a selective synthesis of the unusually sensitive cyclophanic α-pyrone neurymenolide A, the chosen catalysts must be able to distinguish between six different sites of unsaturation, without scrambling any of the skipped π systems. This challenge was met with a new gold-catalyzed pyrone synthesis in combination with a molybdenum-catalyzed ring-closing alkyne metathesis. Copyright
- Cha?adaj, Wojciech,Corbet, Matthieu,Fürstner, Alois
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supporting information; experimental part
p. 6929 - 6933
(2012/09/25)
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- A type III polyketide synthase from Rhizobium etli condenses malonyl CoAs to a heptaketide pyrone with unusually high catalytic efficiency
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A novel type III polyketide synthase (RePKS) from Rhizobium etli produced a heptaketide pyrone using acetyl-CoA and six molecules of malonyl-CoA. Its catalytic efficiency (kcat/Km = 5230 mM-1 min-1) for malonyl CoA was found to be the highest ever reported. Molecular dynamics studies revealed the unique features of RePKS. The Royal Society of Chemistry 2012.
- Jeya, Marimuthu,Kim, Tae-Su,Kumar Tiwari, Manish,Li, Jinglin,Zhao, Huimin,Lee, Jung-Kul
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p. 3103 - 3106
(2013/01/15)
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- Antitumor agents 287. Substituted 4-amino-2H-pyran-2-one (APO) analogs reveal a new scaffold from neo-tanshinlactone with in vitro anticancer activity
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4-Amino-2H-benzo[h]chromen-2-one (ABO) and 4-amino-7,8,9,10-tetrahydro-2H- benzo[h]chromen-2-one (ATBO) analogs were found to be significant in vitro anticancer agents in our previous research. Our continuing study has now discovered a new simplified (monocyclic rather than tricyclic) class of cytotoxic agents, 4-amino-2H-pyran-2-one (APO) analogs. By incorporating various substituents on the pyranone ring, we have established preliminary structure-activity relationships (SAR). Analogs 19, 20, 23, and 26-30 displayed significant tumor cell growth inhibitory activity in vitro. The most active compound 27 exhibited ED50 values of 0.059-0.090 μM.
- Dong, Yizhou,Nakagawa-Goto, Kyoko,Lai, Chin-Yu,Morris-Natschke, Susan L.,Bastow, Kenneth F.,Lee, Kuo-Hsiung
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scheme or table
p. 2341 - 2344
(2011/05/15)
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- Antitumor agents 270. Novel substituted 6-phenyl-4H-furo[3,2-c]pyran-4-one derivatives as potent and highly selective anti-breast cancer agents
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6-Phenyl-4H-furo[3,2-c]pyran-4-one derivatives based on neo-tashinlactone (1) were synthesized and evaluated as novel anti-breast cancer agents. Compounds 10-13, 23, 25, and 27 showed potent inhibition against the SK-BR-3 breast cancer cell line. Importantly, 25 and 27 showed the highest cancer cell line selectivity, being approximately 100-250-fold more potent against SK-BR-3 (ED50 0.28 and 0.44 μM, respectively) compared with other cancer cell lines tested. In addition, 25 displayed low cytotoxicity against normal breast cell lines 184A1 and MCF10A. Compounds 25 and 27 merit further investigation in our continuing program to generate and develop selective anti-breast cancer agents.
- Dong, Yizhou,Shi, Qian,Nakagawa-Goto, Kyoko,Wu, Pei-Chi,Morris-Natschke, Susan L.,Brossi, Arnold,Bastow, Kenneth F.,Lang, Jing-Yu,Hung, Mien-Chie,Lee, Kuo-Hsiung
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scheme or table
p. 803 - 808
(2010/04/26)
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- In vitro precursor-directed synthesis of polyketide analogues with coenzyme a regeneration for the development of antiangiogenic agents
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Polyketide analogues are produced via in vitro reconstruction of a precursor-directed polyketide biosynthetic pathway. Malonyl-CoA synthetase (MCS) was used in conjunction with chalcone synthase (CHS), thereby allowing efficient use of synthetic starter molecules and malonate as extender. Coenzyme-A was recycled up to 50 times. The use of a simple immobilization procedure resulted in up to a 30-fold higher yield of pyrone CHS products than that obtained with the free enzyme solutions.
- Kim, Moon I.I.,Kwon, Seok Joon,Dordick, Jonathan S.
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supporting information; experimental part
p. 3806 - 3809
(2009/12/09)
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- Pyrone polyketides synthesized by a type III polyketide synthase from Drosophyllum lusitanicum
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To isolate cDNAs involved in the biosynthesis of acetate-derived naphthoquinones in Drosophyllum lusitanicum, an expressed sequence tag analysis was performed. RNA from callus cultures was used to create a cDNA library from which 2004 expressed sequence tags were generated. One cDNA with similarity to known type III polyketide synthases was isolated as full-length sequence and termed DluHKS. The translated polypeptide sequence of DluHKS showed 51-67% identity with other plant type III PKSs. Recombinant DluHKS expressed in Escherichia coli accepted acetyl-coenzyme A (CoA) as starter and carried out sequential decarboxylative condensations with malonyl-CoA yielding α-pyrones from three to six acetate units. However, naphthalenes, the expected products, were not isolated. Since the main compound produced by DluHKS is a hexaketide α-pyrone, and the naphthoquinones in D. lusitanicum are composed of six acetate units, we propose that the enzyme provides the backbone of these secondary metabolites. An involvement of accessory proteins in this biosynthetic pathway is discussed.
- Jindaprasert, Aphacha,Springob, Karin,Schmidt, Juergen,De-Eknamkul, Wanchai,Kutchan, Toni M.
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experimental part
p. 3043 - 3053
(2009/04/11)
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- Synthesis of the bis-potassium salts of 5-hydroxy-3-oxopent-4-enoic acids and their use for the efficient preparation of 4-hydroxy-2H-pyran-2-ones and other heterocycles
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5-Hydroxy-3-oxopent-4-enoic acid esters can be efficiently transformed into the stable bis-potassium salts of the corresponding 5-hydroxy-3-oxopent-4-enoic acids, from which the sensitive acids are released in situ, the latter being converted into substit
- Schmidt, Dietmar,Conrad, Juergen,Klaiber, Iris,Beifuss, Uwe
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p. 4732 - 4734
(2007/10/03)
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- Facile syntheses of 2,2-dimethyl-6-(2-oxoalkyl)-1,3-dioxin-4-ones and the corresponding 6-substituted 4-hydroxy-2-pyrones
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A variety of 2,2-dimethyl-6-(2-oxoalkyl)-1,3-dioxin-4-ones 5a-l and the corresponding 6-substituted 4-hydroxy-2-pyrones 3a-l were prepared in high yields under mild reaction conditions by the reaction of 2,2,6-trimethyl-1,3- dioxin-4-one 4 with 1-acylbenz
- Katritzky, Alan R.,Wang, Zuoquan,Wang, Mingyi,Hall, C. Dennis,Suzuki, Kazuyuki
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p. 4854 - 4856
(2007/10/03)
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- Exploiting the reaction flexibility of a type III polyketide synthase through in vitro pathway manipulation
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A synthetic metabolic pathway has been constructed in vitro consisting of the type III polyketide synthase from Streptomyces coelicolor and peroxidases from soybean and Caldariomyces fumago (chloroperoxidase). This has resulted in the synthesis of the pentaketide flaviolin and its dimeric derivative, and a wide range of pyrones and their coupled derivatives with flaviolin, as well as their halogenated derivatives. The addition of acyl-CoA oxidase to the pathway prior to the polyketide synthase resulted in unsaturated pyrone side chains, further broadening the product spectrum that can be achieved. The approach developed in this work, therefore, provides a new model to exploit biocatalysis in the synthesis of complex natural product derivatives. Copyright
- Jeong, Jae-Cheol,Srinivasan, Aravind,Grueschow, Sabine,Bach, Horacio,Sherman, David H.,Dordick, Jonathan S.
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- Pyran-2-ones and 5,6-dihydropyran-2-ones useful for treating hyperplasia and other diseases
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Certain 2H-pyran-2-ones are useful for treating benign prostatic hypertrophy or hyperplasia, prostatic cancer, alopecia, hirsutism, acne vulgaris and seborrhea.
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- Synthesis and in vitro studies of pyrone derivatives as scavengers of active oxygen species
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The antioxidant properties of eleven αpyrones and four γ-pyrones were evaluated by means of three different tests: reduction of the stable free radical, 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide anion scavenging assay and lipid peroxidation assay. In the DPPH test, 6-aryl-5,6-dihydro-4-hydroxypyran2-ones (3) and 4-hydroxypyran-2-one (5f) were the most active derivatives with IC50 values ranging from 36.7 to 394 μmol/1. Potent superoxide anion scavenging properties appeared in derivatives possessing phenol moieties. Thus phenolic pyrones 5e and 5f exhibited a note- worthy activity (IC50 = 0.180 and 0.488 mmol/l, respectively) when reference compound, ascorbic acid, demonstrated only 24 % inhibition at a concentration of 1 mg/ml. In addition derivative 5f significantly inhibited the Fe2+/ADP/ascorbate-induced lipid peroxidation of rat liver microsomes with an IC50 value of 0.069 mmol/l. Due to its multiple mechanism of protective action, compound 5f may be useful for the treatment of oxidative tissue injury in human disease.
- Weber,Coudert,Duroux,Leal,Couquelet,Madesclaire
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p. 877 - 884
(2007/10/03)
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- Synthesis of 6-substituted 4-hydroxy-2-pyrones from aldehydes by addition of an acetoacetate equivalent, Dess-Martin oxidation and subsequent cyclization
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A three step procedure for the synthesis of 6-substituted 4-hydroxy-2-pyrones 2 from aldehydes 1 is described. An acetoacetate equivalent 3 was added to the corresponding aldehyde (10 examples) in a vinylogous Mukaiyama aldol addition (72-99%). The intermediate alcohols 4 were oxidized to the ketones 5 using the Dess-Martin method (67%-quant,). A final thermal cyclization of compounds 5 yielded the title compounds 2 (61-92%; 40-85% overall).
- Bach,Kirsch
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p. 1974 - 1976
(2007/10/03)
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- Synthesis and UV studies of a small library of 6-aryl-4-hydroxy-2- pyrones. A relevant structural feature for the inhibitory property of arisugacin against acetylcholinesterase
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4-Hydroxypyrones belong to an important class of compounds not only because of their medicinal significance, but also because they represent a common structural feature among natural products that are biologically relevant. We describe here preparations of a small library of 6-aryl-4- hydroxy-pyrones which represent structural analogs of the DE-ring of arisugacin, a potent and selective inhibitor against acetylcholinesterase. Given the structural significance of the DE-ring in the inhibitory activity of arisugacin, chemical shifts of relevant protons on the pyrone ring are compared, and distinct features in UV absorptions of these 6-aryl-4-hydroxy- pyrones are described.
- Douglas, Christopher J.,Sklenicka, Heather M.,Shen, Hong C.,Mathias, David S.,Degen, Shane J.,Golding, Geoffrey M.,Morgan, Christopher D.,Shih, Regina A.,Mueller, Kristen L.,Seurer, Lisa M.,Johnson, Erik W.,Hsung, Richard P.
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p. 13683 - 13696
(2007/10/03)
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- TWO LACTONE FORMATION REACTIONS FROM 1,3-DIOXIN-4-ONES HAVING HYDROXYALKYL GROUP AT THE 6-POSITION: DIFFERENCE IN RING OPENING AND CLOSURE
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Two methods (A: ring opening to acylketenes followed by intramolecular ketene trapping and B: methoxide-mediated ring opening followed by cyclization of the hydroxy esters thus formed) have become available for the synthesis of lactones and/or cyclic ethers from 1,3-dioxin-4-ones having 1- 4-hydroxyalkyl group at the 6-position.Mechanism and scope of both methods have been clarified.
- Sato, Masayuki,Sakaki, Jun-ichi,Sugita, Yoshiaki,Yasuda, Sanae,Sakoda, Hiroko,Kaneko, Chikara
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p. 5689 - 5708
(2007/10/02)
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- REACTIVITY OF 4-HYDROXY-2-PYRONES IN THE DIELS-ALDER REACTIONS
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Biphenylcarboxylic acid derivatives, and some tetracyclic bridge cycloadducts have been prepared by Diels-Alder reactions of acetylenic and olefinic dienophiles with 4-hydroxy-6-phenyl-2H-pyran-2-one and its methyl ether derivative.
- Tanyeli, Cihangir,Tarhan, Okan
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p. 2453 - 2460
(2007/10/02)
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- Synthesis and Reaction of 6-Substituted 3-Methoxycarbonyl-4-methylthio-2H-pyran-2-one Derivatives
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Reaction of aryl and styryl methyl ketones 1a-m with dimethyl bis(methylthio)methylenemalonate (2) in the presence of potassium hydroxide in dimethyl sulfoxide gave the corresponding methyl 6-aryl- and 6-styryl-4-methylthio-2-oxo-2H-pyran-3-carboxylates 3
- Tominaga, Yoshinori,Ushirogochi, Atsuyuki,Matsuda, Yoshiro
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p. 1557 - 1567
(2007/10/02)
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- Use of β-Ketocarboxylic Acids for Syntheses of 6-Substituted 4-Hydroxy-2-pyrones and Acyclic β-Diketones
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β-Ketocarboxylic acids including β-ketoglutaric acid half-esters were cyclized by treating them with 1,1'-carbonyl-diimidazole to give 6-substituted 3-acyl-4-hydroxy-2-pyrones in good yields. 5-Aryl-3,5-dioxo-1-pentanoic acid and monomethyl malonate gave 6-aryl-4-hydroxy-2-pyrone and dimethyl β-ketoglutarate, respectively, on similar treatment.Anibin, one of the Aniba alkaloids, was synthesized from 5-(3-pyridyl)-4-hydroxy-2-pyrone.In addition, it was confirmed that reaction of magnesium β-ketocarboxylate with acylimidazolide gave the corresponding acyclic β-diketone in excellent yield.Keywords - β-ketocarboxilic acid; biogenetic-type synthesis; 4-hydroxy-2-pyrone; β-polyketide; β-ketoglutaric acid; dehydroacetic acid; anibin; Aniba alkaloid; 3-acyl-4-hydroxy-2-pyrone; β-diketone.
- Ohta, Shunsaku,Tsujimura, Atsuhiko,Okamoto, Masao
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p. 2762 - 2768
(2007/10/02)
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