- One-Pot Preparation of Pyranoquinolinones by Ytterbium(III) Trifluoromethanesulfonate-Catalyzed Reactions: Efficient Synthesis of Flindersine, N-Methylflindersine, and Zanthosimuline Natural Products
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An efficient synthesis of pyranoquinolinones is achieved by ytterbium(III) triflate-catalyzed reaction of 4-hydroxy-2-quinolones with a variety of α,β-unsaturated aldehydes in moderate yields. This new method has been applied to the synthesis of pyranoqui
- Lee, Yong Rok,Kweon, Hyuk Il,Koh, Wha Soo,Min, Kyung Rak,Kim, Youngsoo,Lee, Seung Ho
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- A DIELS-ALDER ADDUCCT OF N-METHYLFLINDERSINE AND A QUINOLONE QUINONE METHIDE
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A quinolone quinone methide (5; R=Me), prepared from 1,3-dimethyl-4-hydroxy-2-quinolone (7) and DDQ, reacted readily with N-methylflindersine (3) to give a single cyclo-addition product (4).
- Grundon, Michael F.,Ramachandran, V. N.,Sloan, Barbara M.
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- Efficient synthesis of substituted pyranoquinolinones from 2,4-dihydroxyquinoline: Total synthesis of zanthosimuline, cis-3′, 4′-dihydroxy-3′,4′-dihydroflindersine, and orixalone D
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A convenient and efficient synthesis of pyranoquinolinones was achieved using the ethylenediamine diacetate catalyzed reactions of 2,4- dihydroxyquinoline and a variety of α,β-unsaturated aldehydes in good yield. The key feature of these reactions is the
- Wang, Xue,Yong, Rok Lee
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- Soyauxinine, a New Indolopyridoquinazoline Alkaloid from the Stem Bark of Araliopsis soyauxii Engl. (Rutaceae)
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The chemical investigation of the total alkaloid extract (TAE) of the stem bark of Araliopsis soyauxii (Rutaceae) afforded an unreported indolopyridoquinazoline (compound 1) along with nine previously known alkaloids 2-10. In addition, six semi-synthetic derivatives 3a-c, 4b, 5a and 6a were prepared by allylation and acetonidation of soyauxinium nitrate (5), edulinine (3), ribalinine (4) and arborinine (6). The structures and spectroscopic data of five of them are reported herein for the first time. The suggested mechanism for the formation of the new N-allylindolopyridoquinazoline 5a is presented. The structures of natural and derived compounds were determined employing extensive NMR and MS techniques. The absolute configuration of stereogenic centers in compounds 2-4 were determined using NOESY technique and confirmed by the single-crystal X-ray diffraction (SC-XRD) technique. The use of SC-XRD further enabled us to carry out a structural revision of soyauxinium chloride recently isolated from the same plant to soyauxinium nitrate (5). The TAE, fractions, compounds 1-7 and 9, and semi-synthetic derivatives 3a-c, 4b, 5a and 6a were evaluated for their cyto-toxic activity towards the cervix carcinoma cell line KB-3-1. No significant activity was recorded for most of the compounds except for 9, which showed moderate activity against the tested cancer cell lines.
- Atangana, Albert Fouda,Fotso, Ghislain Wabo,Happi, Emmanuel Ngeufa,Lenta, Bruno Ndjakou,Mbahbou, Gabin Thierry Bitchagno,Ngadjui, Bonaventure Tchaleu,Noulala, Cédric Guy Tchatchouang,Ouete, Judith Laure Nantchouang,Sewald, Norbert,Stammler, Hans-Georg
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- Asymmetric Total Synthesis and Biological Evaluation of the Natural PDE4 Inhibitor Toddacoumalone
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We describe herein the first asymmetric total synthesis and biological evaluation of the natural PDE4 inhibitor toddacoumalone and its stereoisomers. The key step of the total synthesis is a formal asymmetric [4 + 2] cycloaddition reaction catalyzed by chiral secondary amine catalysts. A variety of pyranoquinolinones and 3-methylcrotonaldehyde are well tolerated under the optimized reaction conditions, which paved the way for further SAR studies. Further biological evaluation showed 1a′ with the best PDE4 inhibitory activity (IC50 = 0.18 μM).
- Hou, Ke-Qiang,Chen, Xue-Ping,Huang, Yiyou,Chan, Albert S. C.,Luo, Hai-Bin,Xiong, Xiao-Feng
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supporting information
p. 584 - 588
(2020/02/04)
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- Euodenine A: A small-molecule agonist of human TLR4
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A small-molecule natural product, euodenine A (1), was identified as an agonist of the human TLR4 receptor. Euodenine A was isolated from the leaves of Euodia asteridula (Rutaceae) found in Papua New Guinea and has an unusual U-shaped structure. It was synthesized along with a series of analogues that exhibit potent and selective agonism of the TLR4 receptor. SAR development around the cyclobutane ring resulted in a 10-fold increase in potency. The natural product demonstrated an extracellular site of action, which requires the extracellular domain of TLR4 to stimulate a NF-κB reporter response. 1 is a human-selective agonist that is CD14-independent, and it requires both TLR4 and MD-2 for full efficacy. Testing for immunomodulation in PBMC cells shows the induction of the cytokines IL-8, IL-10, TNF-α, and IL-12p40 as well as suppression of IL-5 from activated PBMCs, indicating that compounds like 1 could modulate the Th2 immune response without causing lung damage.
- Neve, Juliette E.,Wijesekera, Hasanthi P.,Duffy, Sandra,Jenkins, Ian D.,Ripper, Justin A.,Teague, Simon J.,Campitelli, Marc,Garavelas, Agatha,Nikolakopoulos, George,Le, Phuc V.,De A. Leone, Priscila,Pham, Ngoc B.,Shelton, Philip,Fraser, Neil,Carroll, Anthony R.,Avery, Vicky M.,McCrae, Christopher,Williams, Nicola,Quinn, Ronald J.
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p. 1252 - 1275
(2014/03/21)
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- Microwave-assisted solvent and catalyst free synthesis of 2H-Pyrans
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This paper describes a simple and efficient method involving domino Knovenegal/6π electrocyclization for the preparation of a variety of 2H-pyrans using microwave irradiation under solvent- and catalyst-free conditions. This method offers the advantages of a green approach, high yields, and short reaction times. Sixteen compounds (9a-p) were obtained in good to excellent yields using the procedure.
- Edayadulla, Naushad,Lee, Yong Rok
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p. 2963 - 2967
(2014/01/06)
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- Green one-pot synthesis of 2h-pyrans under solvent-free conditions catalyzed by ethylenediammonium diacetate
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Ethylenediammonium diacetate readily catalyzes the Knoevenagel-type condensation between 1,3-dicarbonyl substrates and ,-unsaturated aldehydes at room temperature under solvent-free conditions. This rapid, efficient, and convenient one-pot approach to the
- Riveira, Martin J.,Mischne, Mirta P.
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p. 208 - 220,13
(2020/09/02)
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- Synthesis of melicodenines C, D and e
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A synthesis of the unusual cyclobutane-quinolinone alkaloids melicodenines C, D and E by intermolecular [2+2] cycloaddition is described.
- Holla, Harish,Jenkins, Ian D.,Neve, Juliette E.,Pouwer, Rebecca H.,Pham, Ngoc,Teague, Simon J.,Quinn, Ronald J.
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supporting information
p. 7101 - 7103
(2013/01/15)
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- Environmentally benign, one-pot synthesis of pyrans by domino Knoevenagel/6π-electrocyclization in water and application to natural products
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In water medium, environmentally benign, facile, and efficient synthesis of pyrans was achieved in good yields by the reactions of a variety of cyclic 1,3-dicarbonyls with several α,β-unsaturated aldehydes. The key strategy was a formal [3+3] cycloaddition by domino Knoevenagel/6π- electrocyclization. This methodology was applied to the synthesis of biologically interesting pyranocoumarin, pyranoquinolinone, and pyranonaphthoquinone derivatives along with selected natural and non-natural products. The Royal Society of Chemistry 2010.
- Jung, Ene Jin,Park, Byung Ho,Lee, Yong Rok
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experimental part
p. 2003 - 2011
(2011/02/19)
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- Simple efficient synthesis of pyranoquinoline alkaloids: Flindersine, khaplofoline, haplamine and their analogues
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An efficient two step synthesis of pyranoquinoline alkaloids is described. Direct treatment of isoprene with 4-hydroxyquinolin-2(1H)-one in the presence of polyphosphoric acid furnished dihydroflindersine in good yield, and which on dehydrogenation led to a new synthesis of flindersine. Khaplofoline, a linear pyranoquinoline alkaloid, was obtained as a minor product. The syntheses of derivatives are also documented.
- Thangavel, Dhanabal,Ravindran, Sangeetha,Moonsamy, Gengan Robert,Palathurai, Mohan Subramaniam
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p. 124 - 126
(2008/02/11)
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- Efficient one-pot trans-dihydroxylation of 2H-pyrans using dimethyldioxirane (DMD): synthesis of trans-3,4-dihydroxy-3,4-dihydro-O-methyloctandreolones, orixalone D, and trans-3,4-dihydroxy-3,4-dihydromollugin natural products
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An efficient one-pot formation of trans-diols on 2H-pyranyl rings was achieved by dimethyldioxirane in wet acetone. This new methodology was applied to the synthesis of natural products containing trans-diol on the pyranyl rings such as trans-3,4-dihydroxy-3,4-dihydro-O-methyloctandreolones, orixalone D, and trans-3,4-dihydroxy-3,4-dihydromollugin.
- Wang, Xue,Lee, Yong Rok
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p. 6275 - 6280
(2008/02/10)
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- Synthesis of pyranoquinoline alkaloids via (4+2) cycloaddition reaction
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An easy route to synthesize pyranoquinoline based alkaloids like flindersine, haplamine, N-methylflindersine and its derivatives were performed from the respective 4-hydroxyquinolin-2(1H)-one, dimethyl acrylic acid and para formaldehyde through generation of O-quinone methide intermediates and subjecting (4+2) cycloaddition. Further, dihydro intermediates were oxidized by DDQ.
- Suresh,Dhanabal,Nandha Kumar,Mohan
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- Reactions of heterocyclic quinone methides: A facile entry to synthesize the alkaloid, flindersine and its analogues
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A concise synthesis of pyranoquinoline based alkaloids, flindersine, 8-methoxy flindersine and N-methyl flindersine, from the respective 4-hydroxy-3-methyl-2(1H)-quinolines, using 2,3-dichloro-5,6-dicyano-p-benzoquinone and dimethyl acrylic acid generated through quinone methide intermediates is reported.
- Kumar, R. Nandha,Selvi, S. Thamarai,Suresh,Mohan
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p. 187 - 188
(2007/10/03)
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- SRS-A Antagonist pyranoquinolone alkaloids from East African Fagara plants and their synthesis
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Three pyranoquinolone alkaloids isolated from two East African Fagara plants have been found to exhibit SRS-A antagonist action. Their synthesis has been accomplished, using a modified Coppola's method or a thermal cyclization followed by an electrocyclic
- Kamikawa, Tadao,Hanaoka, Yasuyuki,Fujie, Satoru,Saito, Ken,Yamagiwa, Yoshiro,Fukuhara, Katsuya,Kubo, Isao
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p. 1317 - 1320
(2007/10/03)
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- Quinolinone Cycloaddition as a Potential Synthetic Route to Dimeric Quinoline Alkaloids
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Acid-catalysed dehydration of the quinolinone allylic alcohol 24 and concominant Diels-Alder cycloaddition of the resulting diene 25 under acid conditions, followed by further intramolecular cyclization, led to the isolation of isomeric tetracyclic compounds containing one quinolin-2-one and one quinolin-4-one ring (dimer A, 27 and dimer C, 30).Further intramolecular cyclization of dimer A 27 yielded the heptacyclic product (dimer B, 28) having a ring structure of similar type to the dimeric quinoline alkaloids (paraensidimerins).The structures of the cyclization products (dimer a, dimer B and dimer C) have been determined by spectroscopic and X-ray diffraction methods.Mechanistic pathways for the chemical synthesis of polycyclic quinolinone products and their relevance in the biosynthesis of dimeric quinoline alkaloids are discussed.
- Barr, Stephen A.,Neville, Charles F.,Grundon, Michael F.,Boyd, Derek R.,Malone, John F.,Evans, Timothy A.
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p. 445 - 452
(2007/10/02)
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- Heck reactions of 3-iodo-N-methyl-quinolin-2(1H)-ones with 2-methylbut-3-en-2-ol
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Treatment of 4-acetoxy-3-iod-N-methyl-quinolin-2(1H)-one, 3-iod-N-methyl-4-tosyloxy-quinolin-2(1H)-one and 3-iod-4-methoxy-N-methyl-quinolin-2(1H)-one with 2-methylbut-3-en-2-ol under Heck conditions led to the related (E)-3-(3-methylbut-1-en-3-olyl)-derivatives, potential precursors of dimeric quinolines. Dehydration of the tertiary hydroxy group of 4-methoxy-(E)-3-(3-methylbut-1-en-3-olyl)-N-methyl-quinolin-2(1H)-one with acetic acid gave 4-methoxy-(E)-3-(3-methylbut-1,3-dienyl)-N-methyl-quinolin-2(1H)-one.
- Reisch,Iding
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p. 579 - 582
(2007/10/02)
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- Approaches to the syntheses of dimeric quinolinone alkaloids
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A quinolinone allylic alcohol has been synthesised by a palladium-catalysed coupling reaction. Acid-catalysed dehydration of the latter and concomitant Diels-Alder dimerisation, of the resulting diene, afforded dimeric quinolinone derivatives and demonstrated possible approaches to the syntheses of compounds of this type.
- Neville, Charles F.,Barr, Stephen A.,Grundon, Michael F.
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p. 5995 - 5998
(2007/10/02)
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- A simple synthesis of N-methylflindersine
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A simple and convenient four-step synthesis of N-methylflindersine (I) has been accomplished in 46percent overall yield.
- Anand, R C,Sinha, A K
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p. 604 - 605
(2007/10/02)
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- A NEW APPROACH TO HEMITERPENOID TRICYCLIC QUINOLONES. SYNTHESIS OF N-METHYLFLINDERSINE, KHAPLOPHOLINE AND OTHER STRUCTURALLY SIMILAR ALKALOIDS
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A new and general synthesis of tricyclic quinolone alkaloids is described which, by cyclization of 3-butenyl-4-hydroxyquinolones promoted by mercury(II) ion or by formic acid, affords pyranoquinolones and pyranoquinolones, respectively, with regio- and site-selectivity better than those obtained employing known methodologies. 3-Butenyl-4-hydroxyquinolones have been reacted with mercury(II) acetate to give, after work-up, the corresponding 2-(chloromercurymethyl)pyranoquinolones, which have been reductively demercurated with sodium borohydride and then dehydrogenated by treatment with DDQ.Alternatively, from the same starting compounds the "linear" isomers are obtained by formic acid-promoted cyclization.N-Methylflindersine, khaplofoline and other structurally similar alkaloids have been obtained.
- Bravo, Pierfrancesco,Resnati, Giuseppe,Viani, Fiorenza,Cavicchio, Giancarlo
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p. 507 - 512
(2007/10/02)
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- Acetylenchemie. 4 Mitt. Synthese von Haplophyllin und N-Methylflindersin, zwei Wege zu N-funktionalisierten Pyranochinolin-Alkaloiden
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Pyranochinolin-Alkaloide (3), geeignete Vorstufen fuer photobiomimetische Dimerisierungen, sind durch PTC-Reaktion eines 4-Hydroxychinolin-2-ons (1) mit 3-Chlor-3-methylbut-1-in zugaenglich, wobei als Nebenprodukt die Furochinolin-2-on-isomere (5) anfallen.Bei der Synthese von Flindersin (3a) wurde zusaetzlich das Oxazolochinolin-5-on (4) gewonnen; bei der vom N-Methylflindersin (3b) das Bis-(N-methyl-4'-hydroxychinolin-2'-on-3'-yl)-isopenten (7).Alkaloiddimere, deren Bildung aus Intermediaten formulierbar ist, traten nicht auf.Die Entstehung von7 bestaetigt bislang diskutierte Reaktionsablaeufe.Haplophyllin (3c) wurde durch N-Alkylierung von 3a mit 3-Methylcrotonsaeurechlormethylester erstmalig synthetisch dargestellt.
- Reisch, Johannes,Bathe, Andreas,Rosenthal, Bernd H. W.,Salehi-Artimani, Reza A.
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p. 869 - 872
(2007/10/02)
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- A CONVENIENT SYNTHESIS OF FLINDERSINE, ATANINE AND THEIR ANALOGUES
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A new synthesis of the pyranoquinolone alkaloids flindersine (8a), 8-methoxyflindersine (8c), N-methylflindersine (9a), zanthobunglanine (9c), oricine (9d) and veprisine (9e) and the prenylquinolone alkaloids atanine (13a), preskimmianine (13e), N-methylatanine (14a), O-methylglycosolone (14c) and N-methylpreskimmianine (14e) is described.
- Ramesh, M.,Mohan, P. S.,Shanmugam, P.
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p. 4041 - 4050
(2007/10/02)
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