- First total synthesis of the proposed structures of orisuaveolines A and B
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First total synthesis of the proposed structures of β- indoloquinazoline alkaloids orisuaveolines A and B is reported. The key steps of the synthesis included a Pictet-Spengler reaction to build a six-member lactam which further transformed into target molecular by a one-pot condensation. This synthesis provided an access to the proposed structures of orisuaveolines A and B in a short and convenient manner from inexpensive, commercially available starting materials. The structures of our synthesized products were confirmed by 2D-NMR experiments. First total synthesis of the proposed structures of β-indoloquinazoline alkaloids orisuaveolines A and B is reported. The key steps of the synthesis included a Pictet-Spengler reaction to build a six-member lactam which further transformed into target molecular by a one-pot condensation. The structures of our synthesized products were confirmed by 2D-NMR experiments. Copyright
- Zhang, Jie,Da, Shijun,Feng, Xiaolin,Chen, Xiaoyi,Jiang, Jianhui,Li, Ying
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- Access to substituted thiapyrrolizidinones and fused pyridones using the domino N-acyliminium-thionium equilibrium/1,3-dipolar cycloaddition/desulfurization cyclization cascade
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Substituted thiapyrrolizidinones and fused pyridones, and quinolizinones were reported efficaciously from suitable thioamides in yields ranging from 30% to 65%. The reaction proceeded in a one-pot procedure as cascade process by the intramolecular 1,3-dip
- Hamid, Abdulkareem,Oulyadi, Hassan,Da?ch, Adam
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Read Online
- Investigation into the stability and reactivity of the pentacyclic alkaloid dehydroevodiamine and the benz-analog thereof
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Limited synthetic approaches to obtain the biologically active alkaloid dehydroevodiamine (DHED) are known to date. Undesired demethylation in the most widely applied route was found to be a hampering side reaction for the benz-DHED derivative leading to a quinazolinone, which represents a benz-rutaecarpine derivative. For rutaecarpine, a related plant alkaloid, many different synthetic approaches have been described. Alternative reaction procedures to obtain DHED such as methylation of rutaecarpine and oxidation of evodiamine were investigated to make DHED more easily accessible and the latter method proved to be the most successful one. Furthermore, the remarkable equilibrium between the ring closed quinazolinium and the ring open form of the compounds was systematically investigated by UV-vis measurements. The ring open form and the quinazolinium salt, form the same species when incubated in buffer solution for 24 h. A better soluble form, i.e., 'hydroxyevodiamine', seems to represent the biologically active form that has not yet been described.
- Wehle, Sarah,Espargaró, Alba,Sabaté, Raimon,Decker, Michael
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p. 2535 - 2543
(2016/04/26)
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- Optical evodiamine derivatives: Asymmetric synthesis and antitumor activity
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Evodiamine and its derivatives have an asymmetric center at the C13b position. Herein, isomers of evodiamine derivatives 2 and 3 were obtained by straightforward asymmetric total synthesis. Their inhibitory activities toward topoisomerases I and II and th
- Li, Zhen-Gang,Dong, Guo-Qiang,Wang, Sheng-Zheng,Miao, Zhen-Yuan,Yao, Jian-Zhong,Zhang, Wan-Nian,Sheng, Chun-Quan
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p. 267 - 271
(2015/04/14)
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- Fischer Reaction with 2-Perfluoroalkylated Cyclic Imines - An Efficient Route to 2-Perfluoroalkyl-Substituted Tryptamines and Their Derivatives and Homologues
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The reaction of 2-perfluoroalkyl-substituted cyclic imines with arylhydrazines was investigated. We found that 2-perfluoroalkylated cyclic imines are highly reactive electrophiles that form, through ring opening, the corresponding hydrazones bearing an amine group at the end of the alkyl chain. Subsequent acidic treatment resulted in a Fischer rearrangement. Thus, a new synthesis of 2-perfluoroalkylated tryptamines and their homologues through a Fischer reaction was developed. The possibility of modification of the indole core of the 2-CF3-substituted tryptamine products was demonstrated, and various 2-trifluoromethylated tryptamines substituted at the 5-position were prepared. An efficient method for the synthesis of CF3-substituted tryptamines was developed based on the Fischer reaction of perfluoroalkyl-substituted cyclic imines with arylhydrazines. A 5-bromotryptamine was also transformed into further derivatives.
- Shmatova, Olga I.,Shevchenko, Nikolay E.,Nenajdenko, Valentine G.
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supporting information
p. 6479 - 6488
(2015/10/19)
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- 17a-HYDROXYLASE/C17,20-LYASE INHIBITORS
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The present invention provides compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, R6, A and n are as defined herein. A deuteriated derivative of the compound of Formula (I) is also provided.
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- Efficient synthesis of eudistomin U and evaluation of its cytotoxicity
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Eudistomin U is a member of a subclass of naturally occurring indole alkaloids known as β-carbolines. These molecules are reported to have diverse biological activity and high binding affinity to DNA, which make them attractive targets for total synthesis
- Roggero, Chad M.,Giulietti, Jennifer M.,Mulcahy, Seann P.
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supporting information
p. 3549 - 3551
(2014/07/22)
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- Efficient synthesis of eudistomin U and evaluation of its cytotoxicity
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Eudistomin U is a member of a subclass of naturally occurring indole alkaloids known as β-carbolines. These molecules are reported to have diverse biological activity and high binding affinity to DNA, which make them attractive targets for total synthesis
- Roggero, Chad M.,Giulietti, Jennifer M.,Mulcahy, Seann P.
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supporting information
p. 3549 - 3551
(2015/02/19)
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- Synthesis of 3,4-dihydroisoquinolin-1-ones from N-Boc-(β-Arylethyl) carbamates via isocyanate intermediates
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Mild reaction conditions for the regioselective synthesis of isoquinolin-1-ones and related fused-ring heterocycles from N-Boc-protected (β-arylethyl)carbamates are described. The reactions involved the use of Tf2O and 2-chloropyridine and isocyanates are likely to be key intermediates. The method was extended to substrates bearing less nucleophilic aryl moieties by using Lewis acid additives, such as BF3· Et2O, to enhance the Friedel-Crafts-type cyclization of the isocyanate intermediates. This method allowed the synthesis of various substituted isoquinolin-1-ones, β-carbolines, thiophene-fused ring systems and tetrahydrobenzoazepin-1-ones in good yields and with high regioselectivities. Copyright
- In, Jinkyung,Hwang, Soonho,Kim, Changhun,Seo, Jae Hong,Kim, Sanghee
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p. 965 - 971
(2013/03/14)
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- An expedient protecting-group-free total synthesis of (±)- dievodiamine
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The first total synthesis of the Evodia rutaecarpa derived natural product dievodiamine is described. The convergent synthesis was performed without protecting groups, delivering a route that is short and high yielding and uses limited chromatography. Key
- Unsworth, William P.,Kitsiou, Christiana,Taylor, Richard J. K.
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supporting information
p. 3302 - 3305
(2013/07/26)
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- RUTAECARPINE DERIVATIVES FOR ACTIVATING CYP1A2 IN A SUBJECT
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The teachings provided herein generally relate to compositions comprising rutaecarpine derivatives that activates CYP1A2 through enzyme induction. The uses for such a derivative can include removing caffeine from a subject, improving sleep, treating insomnia, treating caffeine toxicity, treating caffeine addiction and withdrawal symptoms, and the like. Caffeine is just one example of a substrate that can be removed using the derivatives taught herein, and other examples, including theophylline, are provided herein.
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- 17α-HYDROXYLASE/C17,20-LYASE INHIBITORS
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The present invention provides compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, R6, A and n are as defined herein. A deuteriated derivative of the compound of Formula (I) is also provided.
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Page/Page column 151
(2012/04/04)
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- Synthesis and cytotoxic evaluation of 1-carboxamide and 1-amino side chain substituted β-carbolines
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The condensation of alkylenediamine with ethyl β-carboline-1- carboxylate and 1-bromo-β-carboline gave β-carboline-1-carboxamides and 1-amino-β-carbolines, respectively. Some of these β-carbolines were active against a panel of human tumor cell lines, and 1-amino derivatives were more potent than their 1-carboxamide congeners. In particular, among the 1-amino-β-carbolines, the N9-arylated alkyl substituted β-carbolines exhibited the most interesting cytotoxic activities with IC50 value of lower than 20 μM. The preliminary structure-activity relationships (SARs) analysis suggested that (1) 1-amino substituents were the advisable pharmacophoric group for enhanced cytotoxic activities; (2) the introduction of appropriate arylated alkyl groups into position-9 of β-carboline facilitated their cytotoxic potencies.
- Ma, Chunming,Cao, Rihui,Shi, Buxi,Zhou, Xiantai,Ma, Qin,Sun, Jie,Guo, Liang,Yi, Wei,Chen, Zhiyong,Song, Huacan
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scheme or table
p. 5513 - 5519
(2010/12/20)
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- Reaction of 3,4-dihydro-β-carbolines with 4-fluorophenyl-nitrile oxide
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The reaction of 3,4-dihydro-β-carboline 5a with the nitrile oxide generated from 4-fluoro-Nhydroxybenzenecarboximidoyl chloride (6) gave novel adduct 7a that on standing at 26 °C in CDCl3 was isomerized to species 8. As an extension, the reacti
- Milena, Matyas,Abranyi-Balogha, Peter,Dancso, Andras,Simig, Gyula,Keglevich, Gyoergy
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p. 377 - 382
(2011/04/12)
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- Efficient synthesis of tetrahydro-b-carbolin-1-one and dihydroisoquinolin- 1-one derivatives as versatile Intermediates
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An efficient one-pot procedure is described in which an isocyanate intermediate, generated from the corresponding carboxylic acid by a modified Curtius rearrangement, is captured by a tethered aromatic ring in the presence of BF3?OEt2 to generate various
- Judd, Katie E.,Mahon, Mary F.,Caggiano, Lorenzo
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experimental part
p. 2809 - 2817
(2010/01/21)
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- Novel inhibitors of acetyl- and butyrylcholinesterase derived from the alkaloids dehydroevodiamine and rutaecarpine
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Derived from the structures of the alkaloids rutaecarpine and dehydroevodiamine (DHED), and the long-known acetylcholinesterase (AChE) inhibitor tacrine, respectively, novel compounds were synthesised, including: 13-methyl-5,8-dihydro-6H-isoquino[1,2-b]quinazolin-13-ium chloride (12), (8Z)-5,6-dihydro-8H-isoquino[1,2-b]quinazolin-8-imine (13), 5,8-dihydro-6H- isoquino[1,2-b]quinazoline (15a), 13-methyl-5,8-dihydro-6H-isoquino[1,2-b] quinazolin-13-ium chloride (16), 5,7,8,13-tetrahydroindolo [2′,3′:3, 4]pyrido[2,1-b]quinazoline (17), and N-(2-phenylethyl)-N-[(12Z)-7,8,9,10- tetrahydroazepino [2,1-b]quinazolin-12(6H)-ylidene]amine (20), respectively. In a first step to evaluate their possible applicability for antiamnesic therapy, the inhibition of AChE and butyrylcholinesterase (BChE) were determined: compounds 13, 15a, 17, and 20 are moderate or strong inhibitors of ChE, the latter two compounds show a 10-fold higher affinity to BChE. Compound 12 is a moderate inhibitor of AChE showing selectivity towards this enzyme. (Chemical presented)
- Decker, Michael
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p. 305 - 313
(2007/10/03)
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- Synthesis and cytotoxic activity of novel quinazolino-β-carboline-5- one derivatives
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A novel series of quinazolino-β-carbolinone derivatives was synthesized and evaluated for their in vitro and in vivo anticancer activity. Many compounds have shown good in vitro activity in the range 1-8μM concentration. Three of the compounds were further tested in nude mice bearing HT-29 colon cancer xenografts.
- Baruah, Bipul,Dasu, Kavitha,Vaitilingam, Balasubramanian,Mamnoor, Premkumar,Venkata, Prasanthi Penubaka,Rajagopal, Sriram,Yeleswarapu, Koteswar Rao
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p. 1991 - 1994
(2007/10/03)
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- N6-Substituted Adenosine Receptor Agonists. Synthesis and Pharmacological Activity as Potent Antinociceptive Agents
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Novel N6-(indol-3-yl)alkyl derivatives of adenosine were synthesized.The adenosine receptor affinity and the antinociceptive activity of these compounds were assessed in binding studies and the phenylbenzoquinone-induced writhing test.Most of these analogues exhibited a potent analgesic activity without side effects.Among them, compound 3c (UP 202-32) bound to A1 (Ki = 110 nM) and A2 (Ki = 350 nM) adenosine receptors in a specific manner since it did not interact with many other receptors, especially opioid binding sites.The antinociceptive activity in the phenylbenzoquinone assay (ED50 = 3.3 mg/kg po) was antagonized by 8-cyclopentyltheophylline, suggesting that an adenosinergic mechanism underlies the analgesic activity observed with this compound.The data obtained with these new N6-substituted adenosine receptor agonists emphasize the interest of such compounds in the treatment of pain.
- Guengoer, Timur,Malabre, Patrice,Teulon, Jean-Marie,Camborde, Francoise,Meignen, Joelle,et al.
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p. 4307 - 4316
(2007/10/02)
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- β-Carboline Alkaloids, I. - Syntheses of 1-Aryl and 1-Alkenyl-β-carbolines by Palladium-Catalyzed Coupling Reactions
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1-Chloro-β-carboline (6) is prepared in three steps starting from tryptamine (3).Palladium-catalyzed coupling reactions of 6 with aryl boronic acids offer an easy access to the alkaloids komaroine (11) and perlolyrine (15).Pavettine (16) is prepared by co
- Bracher, Franz,Hildebrand, Dirk
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p. 1315 - 1320
(2007/10/02)
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- EI and CI Mass Fragmentation of Tryptamine, Tetrahydro-β-carboline and Some of their Derivatives
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EI and CI mass spectra of tryptamine and eleven of its derivatives, as well as those of tetrahydro-β-carboline (1,2,3,4-tetrahydro-9H-pyridoindole, THBC) and twelve of its derivatives were recorded and interpreted.An intense ion, most probably possessing a quinolinium ion structure, is produced from tryptamine derivatives by EI.The retro-Diels-Alder reaction is a prominent EI fragmentation pathway of β-carbolines (BC's), and a bulky 1-substituent is also easily split off.CI causes ammonia expulsion from tryptamine derivatives with a primary amino group in the side-chain; in the case of secondary amines and tryptophan derivatives, (MH)+ is the base peak when methane is used as the reaction gas. (MH)+ is the base peak in the CI spectra of BC derivatives, except in the case of derivatives which have a free carbonyl group, the loss of which often yields the base peak.
- Gynther, Jukka
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p. 433 - 441
(2007/10/02)
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- Synthesis and Serotonin-Receptor Activity of Substituted 1-Oxo-1,2,3,4-tetrahydro-&β-carbolines
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2,3-Dihydroxypyridine is used as a starting material for the synthesis of donor and acceptor substituted 1-oxo-1,2,3,4-tetrahydro-β-carbolines via Fisher indole cyclisation.An alkaloid from Alstonia venenata is prepared.All compounds inclusive strychnocarpine show low affinity to the serotonine receptor. - Key words: 3-Hydroxy-2-pyridone, Strychnocarpine Derivatives, 5-Hydroxytryptamine Receptor Stimulators
- Herdeis, Claus,Bissinger, Gerhard
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p. 785 - 790
(2007/10/02)
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- REACTION OF ARYLHYDRAZINES WITH α-FORMYLBUTYROLACTAM DERIVATIVES
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The Vilsmeier formylation of butyrolactam and N-phenylbutyrolactam has given their α-dimethylaminomethylene derivatives.The reaction of the latter with α-substituted arylhydrazines leads to the formation of 1-oxo-1,2,3,4-tetrahydro-β-carbolines.When unsub
- Tokmakov, G. P.,Zemyanova. T. G.,Grandberg, I. I.
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- Synthesis of Vinca Alkaloids and Related Compounds, XIII. Syntheses Starting from 2-(Ethoxycarbonyl)tryptamine
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The Pictet-Spengler reaction of 2-(ethoxycarbonyl)tryptamine (1) with aldehyde esters 2 and 3 leads to unexpected products (4a and 9a/10a, resp.).The structures of the new compounds were elucidated by spectroscopic and chemical means.
- Kalaus, Gyoergy,Gyoery, Peter,Kajtar-Peredy, Maria,Radics, Lajos,Szabo, Lajos,Szantay, Csaba
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p. 1476 - 1483
(2007/10/02)
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- The Reactions of Some Tetrahydro-β-Carbolines, of Hexahydroazepinoindoles, and of Tetrahydrocarbazolones with Arenesulphonyl Azides
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2,9-Dimethyl-1,2,3,4-tetrahydro-1-oxo-β-carboline and 2,9-dimethyl-1,2,3,4-tetrahydro-β-carboline react with arenesulphonyl azides forming indoline-3-spiropyrrolidines; 2,10-dimethyl-3,4,5,10-tetrahydroazepinoindol-1(2H)-0ne and 2,10-dimethyl-1,2,3
- Bailey, A. Sydney,Vandrevala, Marazban H.
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p. 1512 - 1515
(2007/10/02)
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