- Solid-phase synthesis of isoquinolinones using Bischler-Napieralski cyclization
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A traceless solid-phase synthetic approach to isoquinolinones is described here. This approach allows introducing both electron-donating as well as electron-withdrawing moieties on the benzene nuclei of isoquinolinones with high yields and purities. Isoquinolinone is a structural unit found in many natural products having various important biological activities. A traceless solid-phase synthetic approach has been developed to prepare isoquinolinone derivatives. This approach enables one to synthesize isoquinolinones having various moieties on benzene nuclei and also can produce derivatives with a proton on the amide nitrogen.
- Chern, Meei-Shiou,Li, Wen-Ren
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Read Online
- Enhancement of the carbamate activation rate enabled syntheses of tetracyclic benzolactams: 8-oxoberbines and their 5- And 7-membered C-ring homologues
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A route to the direct amidation of aromatic-ring-tetheredN-carbamoyl tetrahydroisoquinoline substrates was developed. This route enabled general access to 8-oxoberberines and their 5- and 7- membered C-ring homologues. It overcomes the undesired tandem side-reactions that result in the destruction of the isoquinoline backbone, which inevitably occurred under our previously reported superacidic carbamate activation method.
- Kurouchi, Hiroaki
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supporting information
p. 653 - 658
(2021/02/06)
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- Easy Access to 2,4-Disubstituted Cyclopentenones by a Gold(III)-Catalyzed A3-Coupling/Cyclization Cascade
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An efficient and convenient synthesis of 2,4-disubstituted cyclopentenones has been achieved through a Au(III)-catalyzed isomerization-A3-coupling/cyclization cascade. A possible mechanism involving an initial Au(III)-catalyzed isomerization, A3-type coupling, and cyclization via an enol intermediate is postulated.
- Hu, Xiwen,Li, Jian,Liu, Li,Xu, Yue,Zhu, Shangrong
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supporting information
p. 9478 - 9483
(2020/12/21)
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- A versatile approach to 1-oxo-, 1-oxo-3,4-dihydro- and 1,3,4-trioxo isoquinoline alkaloids and first total synthesis of the dimeric 1-oxoisoquinoline alkaloids berbanine and berbidine
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We have worked out a very short approach to 1-oxoisoquinoline alkaloids starting from readily available 2-bromobenzamides utilizing a 2-ethoxyvinylboronate as a C2 building block for introduction of the C-3,C-4 unit of the isoquinoline core. TF
- Schütz, Ramona,Schmidt, Sandra,Bracher, Franz
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- Catalyst-free cyclization of anthranils and cyclic amines: One-step synthesis of rutaecarpine
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An efficient synthesis of a variety of quinazolinone derivatives via a direct cyclization reaction between commercially available anthranils and cyclic amines is described. The developed transformation proceeds with the merits of high step- and atom-efficiency, a broad substrate scope, and good to excellent yields, without additional catalysts, and offers a practical way for the preparation of rutaecarpine and its derivatives with structural diversity.
- Li, Jian,Wang, Zheng-Bing,Xu, Yue,Lu, Xue-Chen,Zhu, Shang-Rong,Liu, Li
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p. 12072 - 12075
(2019/10/14)
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- Light-Driven Intramolecular C?N Cross-Coupling via a Long-Lived Photoactive Photoisomer Complex
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Reported herein is a visible-light-driven intramolecular C?N cross-coupling reaction under mild reaction conditions (metal- and photocatalyst-free, at room temperature) via a long-lived photoactive photoisomer complex. This strategy was used to rapidly prepare the N-substituted polycyclic quinazolinone derivatives with a broad substrate scope (>50 examples) and further exploited to synthesize the natural products tryptanthrin, rutaecarpine, and their analogues. The success of gram-scale synthesis and solar-driven transformation, as well as promising tumor-suppressing biological activity, proves the potential of this strategy for practical applications. Mechanistic investigations, including control experiments, DFT calculations, UV-vis spectroscopy, EPR, and X-ray single-crystal structure of the key intermediate, provides insight into the mechanism.
- Jing, Dong,Lu, Cong,Chen, Zhuo,Jin, Songyang,Xie, Lijuan,Meng, Ziyi,Su, Zhishan,Zheng, Ke
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p. 14666 - 14672
(2019/09/06)
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- A g-C3N4-based heterogeneous photocatalyst for visible light mediated aerobic benzylic C-H oxygenations
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A metal-free heterogeneous photocatalytic system has been developed for highly efficient benzylic C-H oxygenations using oxygen as an oxidant. This visible light mediated oxidation reaction utilizes graphitic carbon nitride (g-C3N4) as a recyclable, nontoxic and low cost photocatalyst. Mild reaction conditions allow for the generation of synthetically and biologically valued isochromannones, phthalides, isoquinolinones, isoindolinones and xanthones from readily accessible alkyl aromatic precursors in good yields. The heterogeneous nature of the g-C3N4 catalytic system enables easy recovery and recycling as well as the use in multiple runs without loss of activity. The synthetic utility of this "green" methodology was further demonstrated by applying in bioactive and drug valued target syntheses.
- Geng, Pengxin,Tang, Yurong,Pan, Guanglong,Wang, Wentao,Hu, Jinchuan,Cai, Yunfei
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p. 6116 - 6122
(2019/11/20)
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- Metal-Free Thermal Activation of Molecular Oxygen Enabled Direct α-CH2-Oxygenation of Free Amines
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Direct oxidation of α-CH2 group of free amines is hard to achieve due to the higher reactivity of amine moiety. Therefore, oxidation of amines involves the use of sophisticated metallic reagents/catalyst in the presence or absence of hazardous oxidants under sensitive reaction conditions. A novel method for direct C-H oxygenation of aliphatic amines through a metal-free activation of molecular oxygen has been developed. Both activated and unactivated free amines were oxygenated efficiently to provide a wide variety of amides (primary, secondary) and lactams under operationally simple conditions without the aid of metallic reagents and toxic oxidants. The method has been applied to the synthesis of highly functionalized amide-containing medicinal drugs, such as O-Me-alibendol and -buclosamide.
- Ghosh, Santanu,Jana, Chandan K.
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p. 260 - 266
(2018/02/19)
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- One-Pot N-Deprotection and Catalytic Intramolecular Asymmetric Reductive Amination for the Synthesis of Tetrahydroisoquinolines
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A one-pot N-Boc deprotection and catalytic intramolecular reductive amination protocol for the preparation of enantiomerically pure tetrahydroisoquinoline alkaloids is described. The iodine-bridged dimeric iridium complexes displayed superb stereoselectivity to give tetrahydroisoquinolines, including several key pharmaceutical drug intermediates, in excellent yields under mild reaction conditions. Three additives played important roles in this reaction: Titanium(IV) isopropoxide and molecular iodine accelerated the transformation of the intermediate imine to the tetrahydroisoquinoline product; p-toluenesulfonic acid contributed to the stereocontrol.
- Zhou, Huan,Liu, Yuan,Yang, Suhua,Zhou, Le,Chang, Mingxin
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supporting information
p. 2725 - 2729
(2017/02/26)
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- Facile synthesis of 5-To 7-membered benzolactam compounds via strongly facilitated electrophilic aromtic substitution reaction
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We employed our system to activate aromatic ring-Tethered carbamate compounds with trifluoromethanesulfonic acid to obtain benzolactams with 5-To 7-membered rings, and examined the substrate scope and limitations of this activation method. In 5-membered ring formation, a halogen group on the aromatic ring did not greatly affect the reaction yield, but other electron-donating groups inhibited the cyclization reaction, and various side-reactions occurred. In 7-membered ring formation, eletron-donating groups on aromatic ring promoted the cyclization reaction, but cyclization of electron-deficient aromatic rings did not proceed well. The 6-membered ring formation reaction showed the greatest substrate generality.
- Kurouchi, Hiroaki,Otani, Yuko,Ohwada, Tomohiko
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p. 705 - 713
(2017/04/10)
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- Supported Gold Nanoparticles for Efficient α-Oxygenation of Secondary and Tertiary Amines into Amides
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Although the α-oxygenation of amines is a highly attractive method for the synthesis of amides, efficient catalysts suited to a wide range of secondary and tertiary alkyl amines using O2as the terminal oxidant have no precedent. This report describes a novel, green α-oxygenation of a wide range of linear and cyclic secondary and tertiary amines mediated by gold nanoparticles supported on alumina (Au/Al2O3). The observed catalysis was truly heterogeneous, and the catalyst could be reused. The present α-oxygenation utilizes O2as the terminal oxidant and water as the oxygen atom source of amides. The method generates water as the only theoretical by-product, which highlights the environmentally benign nature of the present reaction. Additionally, the present α-oxygenation provides a convenient method for the synthesis of18O-labeled amides using H218O as the oxygen source.
- Jin, Xiongjie,Kataoka, Kengo,Yatabe, Takafumi,Yamaguchi, Kazuya,Mizuno, Noritaka
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supporting information
p. 7212 - 7217
(2016/07/06)
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- Synthesis of bis-tetrahydroisoquinolines based on homoveratrylamine and a series of dibasic acids. 3.
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Pyrido- and [1, 4]-oxazinoisoquinolines, bis-tetrahydroisoquinolines, the alkaloid corydaldine, cleavage products, and a series of intermediates were prepared from homoveratrylamine and dibasic acids (glutaric and diglycolic) using a Bischler-Napieralski reaction. Their structures were confirmed using IR and NMR spectra and an x-ray crystal structure analysis.
- Sh.saidov,Mazur,Turgunov,Tashkhodzhaev,Levkovich,Vinogradova
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p. 503 - 510
(2014/08/18)
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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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Paragraph 0700
(2014/03/21)
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- Complementary regioselectivity in Rh(III)-catalyzed insertions of potassium vinyltrifluoroborate via C-H activation: Preparation and use of 4-trifluoroboratotetrahydroisoquinolones
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Potassium vinyltrifluoroborate was found to be an efficient partner with benzamide derivatives for Rh(III)-catalyzed annulations. 4- Trifluoroboratotetrahydroisoquinolones were generated under mild conditions, affording a regioisomerically complementary substitution pattern to other alkenes in related reactions. These new boron-containing building blocks were derivatized by N-arylations, retaining the boron substituent for further elaboration.
- Presset, Marc,Oehlrich, Daniel,Rombouts, Frederik,Molander, Gary A.
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supporting information
p. 1528 - 1531
(2013/06/27)
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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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- Development of 3,4-dihydroisoquinolin-1(2H)-one derivatives for the Positron Emission Tomography (PET) imaging of σ2 receptors
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σ2 Receptors are promising biomarkers for cancer diagnosis given the relationship between the proliferative status of tumors and their density. With the aim of contributing to the research of σ2 receptor Positron Emission Tomography (PET) probes, we developed 2-[3-[6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl]propyl]-3, 4-dihydroisoquinolin-1(2H)-one (3), with optimal σ2 pharmacological properties and appropriate lipophilicity. Hence, 3 served as the lead compound for the development of a series of dihydroisoquinolinones amenable to radiolabeling. Radiosynthesis for compound 26, which displayed the most appropriate σ2 profile, was developed and σ2 specific binding for the corresponding [18F]-26 was confirmed by in vitro autoradiography on rat brain slices. Despite the excellent in vitro properties, [18F]-26 could not successfully image σ2 receptors in the rat brain in vivo, maybe because of its interaction with P-gp. Nevertheless, [18F]-26 may still be worthy of further investigation for the imaging of σ2 receptors in peripheral tumors devoid of P-gp overexpression.
- Abate, Carmen,Selivanova, Svetlana V.,Müller, Adrienne,Kr?mer, Stefanie D.,Schibli, Roger,Marottoli, Roberta,Perrone, Roberto,Berardi, Francesco,Niso, Mauro,Ametamey, Simon M.
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supporting information
p. 920 - 930
(2013/11/19)
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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 107
(2012/04/04)
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- Strategies and synthetic methods directed toward the preparation of libraries of substituted isoquinolines
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Strategies for the production of substituted isoquinoline libraries were developed and explored. Routes involving microwave-assisted variants of the Bischler-Napieralski or Pictet-Spengler reaction allowed for cyclization of substituted β-arylethylamine derivatives. The dihydroisoquinolines and tetrahydroisoquinolines thus generated could then be oxidized to their corresponding isoquinoline analogues. An alternate strategy, however, involving the preparation and activation of isoquinolin-1(2H)-ones is demonstrated to be a more practical, rapid, and efficient route to C1- and C4-substituted isoquinoline libraries.
- Awuah, Emelia,Capretta, Alfredo
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experimental part
p. 5627 - 5634
(2010/11/03)
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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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- Construction of the six- and five-membered aza-heterocyclic units of the isoindoloisoquinolone nucleus by parham-type cyclization sequences - Total synthesis of nuevamine
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An efficient methodology for the synthesis of isoindolo[1,2-α] isoquinolones based on two Parham-type cyclizations allowing the formation of the five- and six-membered nitrogenated rings from carbamate or diacylamine precursors is described. The synthetic potential of this method has been further illustrated by the total synthesis of the alkaloid nuevamine. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.
- Moreau, Anne,Couture, Axel,Deniau, Eric,Grandclaudon, Pierre
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p. 3437 - 3442
(2007/10/03)
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- Activation of iodosobenzene by catalytic tetrabutylammonium iodide and its application in the oxidation of some isoquinoline alkaloids
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Oxidation of N-methyltetrahydroisoquinolines with iodosylbenzene in the presence of a catalytic amount of tetrabutylammonium iodide in various solvents afforded N-methyl-2H-3,4-dihydroisoquinol-1-ones in almost quantitative yields. The application of this finding to the oxidation of other isoquinolines, including tetrahydroisoquinolines, lycorine diacetate, and benzyltetrahydroisoquinolines, also afforded the corresponding lactams in good yields, however, accompanied by a few minor byproducts. Under similar conditions, tetrahydroberberine gave a rearranged compound, berberal, as the major product, accompanied by 8-oxoberberine and berberine.
- Huang, Wei-Jan,Singh, Om V.,Chen, Chung-Hsiung,Chiou, Sheng-You,Lee, Shoei-Sheng
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p. 1069 - 1078
(2007/10/03)
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- An autoxidative approach to 1,2,3,4-tetrahydroisoquinolin-1-one and tetrahydro-β-carbolin-1-one
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Treatment of N-benzyl 1,2,3,4-tetrahydroisoquinoline-1-carboxylate with sodium hydride in N,N-dimethylformamide gives the corresponding N-benzyl 1,2,3,4-tetrahydroisoquinolin-1-one in quantitative yield. The N-benzyl 1,2,3,4-tetrahydro-β-carbolin-1-one is prepared in a similar fashion. The N-deprotection occurred concomitantly with the oxidative decarboxylation when the nitrogen was benzyloxycarbonylated.
- Bois-Choussy, Michèle,De Paolis, Micha?l,Zhu, Jieping
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p. 3427 - 3430
(2007/10/03)
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- Structure-activity studies for a novel series of bicyclic substituted hexahydrobenz[e]isoindole α1A adrenoceptor antagonists as potential agents for the symptomatic treatment of benign prostatic hyperplasia
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In search of a uroselective α1A subtype selective antagonist, a novel series of 6-OMe hexahydrobenz[e]isoindoles attached to a bicyclic heterocyclic moiety via a two-carbon linker was synthesized. It was found that in contrast to the previously described series of tricyclic heterocycles,1 this bicyclic series has very specific requirements for the heterocyclic attachments. The most important structural features contributing to the α1A/α1B selectivity of these compounds were identified. In vitro functional assays for the α1 adrenoceptor subtypes were used to further characterize the most selective compounds, and in vivo models of vascular vs prostatic tone were used to assess uroselectivity. Compound 48 showed the highest degree of selectivity in the radioligand binding assays (56-fold), in the in vitro functional tests (80-fold), and for in vivo prostate selectivity (960-fold).
- Meyer,Altenbach,Bai,Basha,Carroll,Kerwin Jr.,Lebold,Lee,Pratt,Sippy,Tietje,Wendt,Brune,Buckner,Hancock,Drizin
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p. 1971 - 1985
(2007/10/03)
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- Autoxidation of intermediary mesoionic 1,3-oxazolium-5-olates generated from cyclic N-acyl α-amino acids
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Mesoionic 1,3-oxazolium-5-olates (munchnones) react fairly rapidly with oxygen to give the autoxidation products when the C-4 substituent is aromatic. The autoxidation occurred in the munchnones generated from N-acyl tetrahydroisoquinoline-1-carboxylic ac
- Kawase, Masami
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p. 1248 - 1253
(2007/10/03)
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- Synthesis of 3,4-dihydroisoquinolines, 2-alkyl(acyl)-1(2H)-3,4-dihydroisoquinolinones, 2-alkyl-1(2H)-isoquinolinones and 1-alkyl-2(2H)-quinolinones by oxidation with potassium permanganate
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Synthesis of 3,4-dihydroisoquinolines 2, 2-alkyl- 6 and 2-acyl-3,4-dihydro-1(2H)-isoquinolinones 9, 2-alkyl-1(2H)-isoquinolinones 14, N-alkyl-3,4-dihydro-2(2H)-quinolinones 16 and N-alkyl-2(2H)-quinolinones 19 by oxidation of 1,2,3,4-tetrahydroisoquinolines 1, N-alkyl (acyl)iminium salts of 3,4-dihydroisoquinolines 5,8 and isoquinoline 13 as well as of N-alkyl ammonium salts of tetrahydroquinoline 15 and quinoline 18 with potassium permanganate is described.
- Venkov,Statkova-Abeghe
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p. 1451 - 1460
(2007/10/03)
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- Unusual Formation of Tetrahydro-1-isoquinolones from Tetrahydroisoquinoline-1-carboxylic Acids with Carbodiimides and Mechanistic Aspects
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The reaction of tetrahydroisoquinoline-1-carboxylic acids with carbodiimides leads to the formation of tetrahydro-1-isoquinolones in high yields, involving a reaction between mesoionic 1,3-oxazol-5-one intermediates and molecular oxygen.
- Kawase, Masami
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p. 1328 - 1329
(2007/10/02)
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- New Facile Synthesis of Isoquinolone Alkaloids
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Beckmann rearrangement of substituted indanone oximes (IIa, b) with PPA gives corydaldine (IIIa) and noroxyhydrastinine (IIIb) which on methylation yield N-methylcorydaldine (IVa) and N-methylnoroxyhydrastinine (IVb) respectively.
- Joshi, Vidya,Hari, M. I.
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- NEW SYNTHESIS OF ISOQUINOLINE ALKALOIDS, THALIFOLINE, CORYPALLINE, AND CHERYLLINE
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Isoquinoline alkaloids, thalifoline, corypalline, and cherylline, were synthesised by application of the cyclisation reaction of β-phenyl-ethyl isocyanate to N-methylisoquinoline lactam with Magic Methyl and the regioselective cleavage reaction of aromatic methoxyl groups with methionine and methanesulphanic acid.
- Irie, Hiroshi,Shiina, Ayako,Fushimi, Tamaki,Katakawa, Jun'ichi,Fujii, Nobutaka,Yajima, Haruaki
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p. 875 - 878
(2007/10/02)
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- STEREOSPECIFIC SYNTHESIS OF SOME POLYCYCLIC CIS-β-LACTAMS
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Amides 1 on reaction with P2S5 in pyridine give thioamides 2 which on treatment with methyl iodide afford the corresponding 1-methylthio-3,4-dihydroisoquinolines 3.Annelation of these imines with phenoxyacetyl chloride in the presence of triethylamine furnish 6-methylthio-7-phenoxy-2',3'-dimethoxybenzooctem 4a and 6-methylthio-7-phenoxy-2',3'-methylenedioxybenzooctem 4b respectively.Desulphurisation of these β-methylthio-β-lactams with Raney nickel yield the novel polycylic cis-β-lactams 5a and 5b.
- Sharma, S. D.,Mehra, Usha,Gupta, P. K.
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p. 3427 - 3430
(2007/10/02)
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