- An improved synthesis of canthin-6-one
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An improved route has been devised which provides canthin-6-one in the highest yield from tryptamine to date. Tryptamine is converted to Nb-benzyltryptamine via reaction with benzoylchloride and reduction using LAH. Pictet-Spengler condensation with 2-ketoglutaric acid, removal of the protecting group by CTH, and aromatization with MnO2 affords canthin-6-one in 48% overall yield.
- Czerwinski, Kevin M.,Zificsak, Craig A.,Stevens, John,Oberbeck, Melissa,Randlett, Christopher,King, Melissa,Mennen, Steve
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- Sequential acid/base-catalyzed polycyclization of tryptamine derivatives. A rapid access to Buechi's ketone
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(Chemical Equation Presented) The development of an efficient and diastereoselective methodology that allows the rapid construction of the tetracyclic core of the Aspidosperma and Strychnos alkaloid families is decribed. Our approach relies upon two key steps: a sequential silica gel/potassium tert-butoxide polycyclization of a tryptamine precursor and a tandem oxidative decarboxylation/ring-closing reaction. The assembly of Buechi's ketone, a key intermediate in the synthesis of vindorosine, has been accomplished using this approach.
- Heureux, Nicolas,Wouters, Johan,Marko, Istvan E.
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- A simple and efficient method for constructing azepino[4,5-b]indole derivatives via acid catalysis
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A new synthetic methodology has been developed to prepare the biologically important azepino[4,5-b]indole derivatives under Br?nsted acid catalysis. The notable features of this protocol include its operational simplicity, high reaction yields and environmentally benign and mild reaction conditions.
- Kumar Boominathan, Siva Senthil,Reddy, Mutra Mohana,Hou, Ruei-Jhih,Chen, Hui-Fen,Wang, Jeh-Jeng
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- Synthesis of ajmalicine derivatives using Wittig-Horner and Knoevenagel reactions
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2-(2,3,4,9-Tetrahydro-1H-β-carbolin-1-yl)acetaldehyde, synthesized from tryptamine in five steps, is easily homologated by Wittig-Horner or Knoevenagel reactions to substituted acrylates. These highly reactive compounds are key intermediates in the synthesis of analogs of the natural indol alkaloid ajmalicine.
- Boumendjel, Ahcene,Nuzillard, Jean-Marc,Massiot, Georges
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- Synthesis, in vitro antibacterial activities of a series of 3-N-substituted canthin-6-ones
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An improved synthetic route of canthin-6-one was accomplished. To further enhance the antibacterial potency and improve water solubility, a series of 3-N-alkylated and 3-N-benzylated canthin-6-ones were designed and synthesized, and their in vitro antibacterial activities were evaluated. A clear structure-activity relationship with peak minimal inhibitory concentration (MIC) values of 0.98 (μg·mL-1) was investigated. Particularly, compounds 6i-r and 6t were found to be the most potent compounds with minimal inhibitory concentration (MIC) values lower than 1.95 (μg·mL-1) against Staphylococcus aureus.
- Dai, Jiang-Kun,Dan, Wen-Jia,Li, Na,Du, Hong-Tao,Zhang, Ji-Wen,Wang, Jun-Ru
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- Gold-Catalyzed Carboamination of Allenes by Tertiary Amines Proceeding with Benzylic Group Migration
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Tertiary amines bearing a benzyl-type group (CH2Ar) undergo Au(I)-catalyzed intramolecular addition to allenes. A formal 1,3-transfer of the CH2Ar group takes place during the cyclization. As demonstrated by both experimental and DFT studies, these unprecedented intramolecular carboaminations involve two consecutive [3,3] rearrangements via a dearomatized intermediate. Because of the poor stability of the enamine products, protocols were developed to convert them in situ to more stable polycyclic chiral compounds. (Figure presented.).
- Milcendeau, Pierre,Gandon, Vincent,Guinchard, Xavier
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- Asymmetric Total Synthesis of (-)-Arborisidine and (-)-19-epi-Arborisidine Enabled by a Catalytic Enantioselective Pictet-Spengler Reaction
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A five-step total synthesis of arborisidine, a caged pentacyclic monoterpene indole alkaloid, has been accomplished in both racemic and enantioselective manners. The synthesis features the following three key steps: (a) a regioselective Pictet-Spengler reaction of tryptamine with 2,3-pentanedione; (b) a chemo-and stereoselective intramolecular oxidative cyclization; and (c) a complexity-generating aza-Cope/Mannich cascade followed by in situ oxidation and epimerization. A chiral pyrenylpyrrolidino-squaramide catalyzed enantioselective Pictet-Spengler reaction between tryptamine and 2,3-pentanedione is subsequently uncovered, allowing us to develop a five-step asymmetric synthesis of (-)-Arborisidine, an enantiomer of the natural substance. Both (±)-19-epi-Arborisidine and (-)-19-epi-Arborisidine are also synthesized, which undergo epimerization at room temperature in the presence of aqueous 2 N KOH to (±)-Arborisidine and (-)-Arborisidine, respectively. The 19-epi-isomer is also partially epimerized to arborisidine upon preparative TLC purification (eluent: MeOH/CHCl3 saturated with NH3) and equilibrium studies indicate that arborisidine is thermodynamically more stable than its 19-epimer. In line with Kam's biosynthesis proposal and their purification protocol, we suspect that 19-epi-Arborisidine could also be a natural product.
- Andres, Rémi,Wang, Qian,Zhu, Jieping
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- BF3·Et2O as a metal-free catalyst for direct reductive amination of aldehydes with amines using formic acid as a reductant
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A versatile metal- and base-free direct reductive amination of aldehydes with amines using formic acid as a reductant under the catalysis of inexpensive BF3·Et2O has been developed. A wide range of primary and secondary amines and diversely substituted aldehydes are compatible with this transformation, allowing facile access to various secondary and tertiary amines in high yields with wide functional group tolerance. Moreover, the method is convenient for the late-stage functionalization of bioactive compounds and preparation of commercialized drug molecules and biologically relevant N-heterocycles. The procedure has the advantages of simple operation and workup and easy scale-up, and does not require dry conditions, an inert atmosphere or a water scavenger. Mechanistic studies reveal the involvement of imine activation by BF3and hydride transfer from formic acid.
- Fan, Qing-Hua,Liu, Xintong,Luo, Zhenli,Pan, Yixiao,Xu, Lijin,Yang, Ji,Yao, Zhen,Zhang, Xin
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supporting information
p. 5205 - 5211
(2021/07/29)
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- Fe-Catalyzed Pictet-Spengler-Type Cyclization via Selective Four-Electron Reductive Functionalization of CO2
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Herein, we describe a novel catalytic Pictet-Spengler-type cyclization using CO2 as a nontoxic and sustainable C1 feedstock with environmentally benign and non-precious-metal iron as catalyst. The reaction is achieved by selective four-electron reduction of CO2 into methylene level intermediate through carefully tuning the reaction parameters. A variety of tetrahydro-β-carbolines and other nitrogen-containing heterocycles can be easily obtained under mild conditions. Mechanistic studies have shown that tetrahydro-β-carbolines are probably obtained via spiroindolenine intermediates.
- Li, Wen-Duo,Chen, Jie,Zhu, Dao-Yong,Xia, Ji-Bao
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supporting information
p. 614 - 620
(2021/02/12)
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- Selective construction of alkaloid scaffolds by alcohol-based direct and mild aerobic oxidative Pictet-Spengler reactions
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Employing TBN/TEMPO as the catalysts and oxygen as the oxidant, the biologically and pharmaceutically significant tetrahydro-β-carboline and β-carboline alkaloid scaffolds that used to be obtained by multi-step processes can now be selectively obtained in only one-stepviadirect aerobic oxidative Pictet-Spengler reactions of tryptamines with alcohols under mild conditions, with water generated as the byproduct. In this reaction, TBN/TEMPO was interestingly found to be able to facilitate the cyclization step of the whole reaction. This method tolerates a variety ofC- andN-substituted tryptamines, and both the more reactive benzylic and allylic alcohols and the less reactive aliphatic alcohols. This method can also be extended to dihydro-β-carboline synthesis and applied to the more available and more economical tryptophan for β-carboline synthesis, revealing its broad substrate scope and potential in synthetic applications.
- Han, Feng,Li, Huan,Liu, Haicheng,Liu, Jianping,Xu, Qing
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supporting information
p. 7079 - 7085
(2020/10/02)
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- CATALYTIC SYSTEMS FOR STEREOSELECTIVE SYNTHESIS OF CHIRAL AMINES BY ENANTIODIVERGENT RADICAL C-H AMINATION
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In one aspect, the disclosure relates to a mode of asymmetric induction in radical processes based on sequential combination of enantiodifferentiative H-atom abstraction and stereoretentive radical substitution. Also disclosed is an asymmetric system for stereoselective synthesis of strained 5-membered cyclic sulfamides via radical 1,5-C—H amination of sulfamoyl azides. The disclosed metalloradical system can control the degree and sense of asymmetric induction in the catalytic radical C—H amination in a systematic manner. The disclosed system is applicable to a broad scope of substrates with different types of C(sp3)-H bonds and exhibits reactivity and selectivity, providing access to both enantiomers of useful 5-membered cyclic sulfamides in a highly enantioenriched form. Also disclosed are catalysts useful in these processes. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.
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Paragraph 0201; 0242; 0244-0245; 0248-0249; 0254
(2020/11/27)
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- Ruthenium Catalyzed Tandem Pictet-Spengler Reaction
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We report a pyridyl-phosphine ruthenium(II) catalyzed tandem alcohol amination/Pictet-Spengler reaction sequence to synthesize tetrahydro-β-carbolines from an alcohol and tryptamine. Our conditions use a Lewis acid cocatalyst, In(OTf)3, that is compatible with typically base catalyzed amination and an acid catalyzed Pictet-Spengler cyclization. This method proceeds well with benzylic alcohols, heterocyclic carbinols, and aliphatic alcohols. We also show how combining this reaction with a subsequent cycloamination enables a direct synthesis of tetracyclic alkaloids like harmicine.
- Cherepakhin, Valeriy,Nalikezhathu, Anju,Williams, Travis J.
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supporting information
(2020/07/15)
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- Pd/Cu Cocatalyzed Oxidative Tandem C-H Aminocarbonylation and Dehydrogenation of Tryptamines: Synthesis of Carbolinones
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The Pd/Cu cocatalyzed oxidative tandem C-H aminocarbonylation and dehydrogenation was developed, affording carbolinones with molecular oxygen as the terminal oxidant. Natural product strychnocarpine and its derivatives were prepared conveniently using this strategy.
- Han, Hui,Xia, Ji-Bao,Yang, Shang-Dong
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p. 3357 - 3369
(2019/04/06)
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- Site-Selective Carbonylative Synthesis of Structurally Diverse Lactams from Heterocyclic Amines with TFBen as the CO Source
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A palladium-catalyzed site-selective C-H carbonylation of heterocyclic amines for the synthesis of lactam motifs has been developed. The reaction of 3-thiophene methylamines, 2-thiophene methylamines, and tryptamines with benzene-1,3,5-triyl triformate (TFBen) as the CO source provides a series of structurally diverse lactams in moderate to high yields with excellent regioselectivities.
- Ying, Jun,Gao, Qian,Wu, Xiao-Feng
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p. 14297 - 14305
(2019/11/03)
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- Metal-Free Dearomatization: Direct Access to Spiroindol(en)ines in Batch and Continuous-Flow
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A metal-free, phosphine-catalyzed intramolecular “umpolung Michael addition” on alkynes to form spiroindol(en)ines is reported. This nucleophilic catalysis enables the formation of a wide scope of five- and six-membered spiroindol(en)ines in moderate to excellent yields in batch as well as under continuous-flow conditions. Triphenylphosphine-catalyzed nucleophilic activation of alkynes allows the exclusive formation of exo-product under mild reaction conditions.
- Ranjan, Prabhat,Ojeda, Gerardo M.,Sharma, Upendra K.,Van der Eycken, Erik V.
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supporting information
p. 2442 - 2446
(2019/01/29)
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- Asymmetric Induction and Enantiodivergence in Catalytic Radical C-H Amination via Enantiodifferentiative H-Atom Abstraction and Stereoretentive Radical Substitution
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Control of enantioselectivity remains a major challenge in radical chemistry. The emergence of metalloradical catalysis (MRC) offers a conceptually new strategy for addressing this and other outstanding issues. Through the employment of D2-symmetric chiral amidoporphyrins as the supporting ligands, Co(II)-based MRC has enabled the development of new catalytic systems for asymmetric radical transformations with a unique profile of reactivity and selectivity. With the support of new-generation HuPhyrin chiral ligands whose cavity environment can be fine-tuned, the Co-centered d-radicals enable to address challenging issues that require exquisite control of fundamental radical processes. As showcased with asymmetric 1,5-C-H amination of sulfamoyl azides, the enantiocontrol of which has proven difficult, the judicious use of HuPhyrin ligand by tuning the bridge length and other remote nonchiral elements allows for controlling both the degree and sense of asymmetric induction in a systematic manner. This effort leads to successful development of new Co(II)-based catalytic systems that are highly effective for enantiodivergent radical 1,5-C-H amination, producing both enantiomers of the strained five-membered cyclic sulfamides with excellent enantioselectivities. Detailed deuterium-labeling studies, together with DFT computation, have revealed an unprecedented mode of asymmetric induction that consists of enantiodifferentiative H-atom abstraction and stereoretentive radical substitution.
- Lang, Kai,Torker, Sebastian,Wojtas, Lukasz,Zhang, X. Peter
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supporting information
p. 12388 - 12396
(2019/08/20)
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- Fast continuous alcohol amination employing a hydrogen borrowing protocol
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A continuous flow method for the direct conversion of alcohols to amines via a hydrogen borrowing approach is reported. The method utilises a low loading (0.5%) of a commercial catalyst system ([Ru(p-cymene)Cl2]2 and DPEPhos), reagent grade solvent and is selective for primary alcohols. Successful methylation of amines using methanol and the direct dimethylamination of alcohols using commercial dimethylamine solution are reported. The synthesis of two pharmaceutical agents Piribedil (5) and Buspirone (25) were accomplished in good yields employing these new methods.
- Labes, Ricardo,Mateos, Carlos,Battilocchio, Claudio,Chen, Yiding,Dingwall, Paul,Cumming, Graham R.,Rincón, Juan A.,Nieves-Remacha, Maria José,Ley, Steven V.
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supporting information
p. 59 - 63
(2019/01/11)
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- Dehydrative Mannich-Type Reaction for the Synthesis of Azepinobisindole Alkaloid Iheyamine A
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A concise synthesis of the azepinobisindole alkaloid iheyamine A from an indole-2,3-epoxide equivalent has been achieved. This method features a formal C3 electrophilic reaction of an indole-2,3-epoxide equivalent with tryptamine to form a 3-aminoindoline and a novel In-catalyzed dehydrative Mannich-type reaction of the hemiaminal to give the azepinobisindole core.
- Abe, Takumi,Yamada, Koji
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supporting information
p. 1469 - 1472
(2018/03/09)
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- Identification of a Potent Tryptophan-Based TRPM8 Antagonist with in Vivo Analgesic Activity
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TRPM8 has been implicated in nociception and pain and is currently regarded as an attractive target for the pharmacological treatment of neuropathic pain syndromes. A series of analogues of N,N′-dibenzyl tryptamine 1, a potent TRPM8 antagonist, was prepared and screened using a fluorescence-based in vitro assay based on menthol-evoked calcium influx in TRPM8 stably transfected HEK293 cells. The tryptophan derivative 14 was identified as a potent (IC50 0.2 ± 0.2 nM) and selective TRPM8 antagonist. In vivo, 14 showed significant target coverage in both an icilin-induced WDS (at 1-30 mg/kg s.c.) and oxaliplatin-induced cold allodynia (at 0.1-1 μg s.c.) mice models. Molecular modeling studies identified the putative binding mode of these antagonists, suggesting that they could influence an interaction network between the S1-4 transmembrane segments and the TRP domains of the channel subunits. The tryptophan moiety provides a new pharmacophoric scaffold for the design of highly potent modulators of TRPM8-mediated pain.
- Bertamino, Alessia,Iraci, Nunzio,Ostacolo, Carmine,Ambrosino, Paolo,Musella, Simona,Di Sarno, Veronica,Ciaglia, Tania,Pepe, Giacomo,Sala, Marina,Soldovieri, Maria Virginia,Mosca, Ilaria,Gonzalez-Rodriguez, Sara,Fernandez-Carvajal, Asia,Ferrer-Montiel, Antonio,Novellino, Ettore,Taglialatela, Maurizio,Campiglia, Pietro,Gomez-Monterrey, Isabel
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p. 6140 - 6152
(2018/07/05)
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- Cantffln - 6 - quaternary ammonium salt and its preparation method and application
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The invention relates to a canthium dicoccum-6-one quaternary ammonium salt and a preparation method and an application thereof. The structural formula of the compound is shown in a formula (1) in the specification, wherein R is ethyl, propyl, isopropyl, allyl, normal-butyl, isobutyl, normal-amyl, normal-octyl, unsubstituted benzyl or substituted benzyl substituted by a hydrogen atom, methyl, bromomethyl, trifluoromethyl, benzyloxyl, a fluorine atom or a chlorine atom; X is chlorine, bromine or iodine. The application is that of the compound for preparing antibacterial drugs.
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Paragraph 0033-0035
(2017/12/02)
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- A Base and Solvent-Free Ruthenium-Catalyzed Alkylation of Amines
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A (pyridyl)phosphine-ligated ruthenium(II) catalyst is reported for the chemoselective benzylic N-alkylation of amines, via a hydrogen-borrowing mechanism. The catalyst operates under mild conditions, neat, and without a base or other additive. These conditions offer remarkable functional group compatibility for applications in organic synthesis, including reactions involving phenols and anilines, which are very difficult to achieve. Mechanistic studies suggest that, unlike other catalysts for this reaction, the redox steps are fast and reversible while imine formation is slow. We perceive that this is the origin of the selectivity realized with these reaction conditions.
- Celaje, Jeff Joseph A.,Zhang, Xingyue,Zhang, Forrest,Kam, Lisa,Herron, Jessica R.,Williams, Travis J.
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p. 1136 - 1142
(2017/08/09)
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- An efficient catalytic reductive amination: A facile one-pot access to 1,2-dihydropyrrolo[3,4-b]indol-3(4H)-ones by using B(C 6 F 5 ) 3 /NaBH 4
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An efficient combination of B(C6F5)3 and NaBH4 was developed for direct reductive amination of aldehydes. A wide range of functional groups such as ester, nitro, nitrile, halogen, alkene, heterocycles were tolerated. Also, acid sensitive protecting groups like TBDMS and TBDPS were not affected. In addition, the present methodology was extended for tandem amination-amidation of 3-formyl-indole-2-carboxylic acids with substituted anilines to afford 1,2-dihydropyrrolo[3,4-b]indol-3(4H)-ones. [Figure not available: see fulltext.]
- Nagarsenkar, Atulya,Prajapti, Santosh Kumar,Babu, Bathini Nagendra
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p. 711 - 716
(2015/06/17)
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- Investigation of the synthesis of benzofuroindolines from N-hydroxyindoles: An O-arylation/[3,3]-sigmatropic rearrangement sequence
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Abstract We report the demonstration that sensitive N-hydroxyindoles can be O-arylated under transition-metal-free conditions with biaryliodonium salts. The subsequent spontaneous [3,3]-sigmatropic rearrangement delivers benzofuroindolines derived from tryptamine. We also describe the practical synthesis of N-hydroxyindoles by oxidation of indolines with m-CPBA.
- Tomakinian, Terry,Kouklovsky, Cyrille,Vincent, Guillaume
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supporting information
p. 1269 - 1275
(2015/06/02)
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- Unified Approach to the Spiro(pyrrolidinyl-oxindole) and Hexahydropyrrolo[2,3-b]indole Alkaloids: Total Syntheses of Pseudophrynamines 270 and 272A
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The first enantioselective total syntheses of architecturally interesting prenylated pyrroloindole alkaloids, (-)-pseudophrynamines 272A (3d) and 270 (3b), have been achieved starting from enantioenriched 2-oxindoles having all-carbon quaternary stereocenters. A common strategy involving a thio-urea catalyzed aldol reaction is employed for the total synthesis of both spiro(pyrrolidinyl-oxindole) and hexahydropyrrolo[2,3-b]indole alkaloids.
- De, Subhadip,Das, Mrinal Kanti,Bhunia, Subhajit,Bisai, Alakesh
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supporting information
p. 5922 - 5925
(2015/12/11)
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- Iridium-catalyzed direct synthesis of tryptamine derivatives from indoles: Exploiting N-protected β-amino alcohols as alkylating agents
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The selective C3-alkylation of indoles with N-protected ethanolamines involving the "borrowing hydrogen" strategy is described. This method provides convenient and sustainable access to several tryptamine derivatives.
- Bartolucci, Silvia,Mari, Michele,Bedini, Annalida,Piersanti, Giovanni,Spadoni, Gilberto
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p. 3217 - 3222
(2015/03/30)
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- Optimization of rutaecarpine as ABCA1 up-regulator for treating atherosclerosis
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ATP-binding cassette transporter A1 (ABCA1) is a key transporter and receptor in promoting cholesterol efflux, and increasing the expression level of ABCA1 is antiatherogenic. In our previous study, rutaecarpine (RUT) was found to protect ApoE-/- mice from developing atherosclerosis through preferentially up-regulating ABCA1 expression. In the present work, a series of RUT derivatives were synthesized and examined as ABCA1 expression up-regulators. Compounds CD1, CD6, and BCD1-2 were found to possess the most potential activity as antiatherosclerotic agents among all compounds tested.
- Li, Yongzhen,Feng, Tingting,Liu, Peng,Liu, Chang,Wang, Xiao,Li, Dongsheng,Li, Ni,Chen, Minghua,Xu, Yanni,Si, Shuyi
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supporting information
p. 884 - 888
(2014/09/17)
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- An efficient palladium-catalyzed N-alkylation of amines using primary and secondary alcohols
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PdCl2 in the presence of dppe or Xantphos(t-Bu) as the ligand is found to be an efficient catalyst for the N-alkylation of various primary and cyclic secondary amines using primary alcohols at 90-130 C under neat conditions. Interestingly, good to excellent yields were achieved when more challenging secondary alcohols were used as alkylating agents at 130-150 C. The reaction could be easily scaled up, as demonstrated for a 10 mmol scale achieving yields up to 90% with a TON of 900.
- Dang, Tuan Thanh,Ramalingam, Balamurugan,Shan, Siah Pei,Seayad, Abdul Majeed
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p. 2536 - 2540
(2013/11/19)
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- Synthesis of substituted amines and isoindolinones: Catalytic reductive amination using abundantly available AlCl3/PMHS
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AlCl3 has been employed for highly chemoselective reductive amination of carbonyl compounds in ethanol using polymethylhydrosiloxane as an inexpensive, stable and safe reducing agent without an inert atmosphere. A large range of functional groups such as nitro, carboxylic acid, acetyl, nitrile, halogen, methoxy, alkene and heterocycles were well tolerated. AlCl3 also catalyzed tandem amination-amidation of 2-carboxybenzaldehyde with different amines to afford N-substituted isoindolinones. The catalyst can be recycled at least three times without any significant effect on activity and selectivity.
- Kumar, Vishal,Sharma, Sushila,Sharma, Upendra,Singh, Bikram,Kumar, Neeraj
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p. 3410 - 3414
(2013/01/16)
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- Syntheses of strychnine, norfluorocurarine, dehydrodesacetylretuline, and valparicine enabled by intramolecular cycloadditions of Zincke aldehydes
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A full account of the development of the base-mediated intramolecular Diels-Alder cycloadditions of tryptamine-derived Zincke aldehydes is described. This important complexity-generating transformation provides the tetracyclic core of many indole monoterpene alkaloids in only three steps from commercially available starting materials and played a key role in short syntheses of norfluorocurarine (five steps), dehydrodesacetylretuline (six steps), valparicine (seven steps), and strychnine (six steps). Reasonable mechanistic possibilities for this reaction, a surprisingly facile dimerization of the products, and an unexpected cycloreversion to regenerate Zincke aldehydes under specific conditions are also discussed.
- Martin, David B. C.,Nguyen, Lucas Q.,Vanderwal, Christopher D.
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scheme or table
p. 17 - 46
(2012/02/04)
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- Synthesis of tetrahydro-β-carbolines via isomerization of N-allyltryptamines: A metal-catalyzed variation on the Pictet-Spengler theme
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An efficient and broadly applicable alternative to the classical Pictet-Spengler synthesis of tetrahydro-β-carbolines is presented. The method relies on metal-catalyzed isomerization of allylic amines to form reactive iminium intermediates which can be trapped by a tethered indole nucleophile. The Royal Society of Chemistry 2012.
- Ascic, Erhad,Hansen, Casper L.,Le Quement, Sebastian T.,Nielsen, Thomas E.
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supporting information; experimental part
p. 3345 - 3347
(2012/05/04)
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- Highly enantioselective pictet-spengler reaction catalyzed by SPINOL-phosphoric acids
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Chiral SPINOL-phosphoric acids are highly enantioselective catalysts for the asymmetric Pictet-Spengler reaction of Nb-α-naphthylmethyl tryptamines with a series of aliphatic and aromatic aldehydes, affording optically active tetrahydro-β-carbolines in excellent yields and ee values. The current protocol has been applied in the asymmetric total synthesis of (-)-harmicine. Copyright
- Huang, Dan,Xu, Fangxi,Lin, Xufeng,Wang, Yanguang
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supporting information; experimental part
p. 3148 - 3152
(2012/04/17)
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- Design and synthesis of Pictet-Spengler condensation products that exhibit oncogenic-RAS synthetic lethality and induce non-apoptotic cell death
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A series of Pictet-Spengler condensation derivatives (tetrahydro-β- carbolines) was designed, synthesized and evaluated for lethality against a panel of seven cancer cell lines. Seven compounds (2a, 13, 20, 21, 27, 29 and 34) showed lethality in at least five cell lines. Among these, compound 27 showed a unique selectivity towards oncogenic-RAS expressing BJ-TERT/LT/ST/RASV12 tumor cells, compared to non-transformed BJ-TERT cells. Further investigation revealed that 27 induces cell death without activation of caspases. This represents a useful new probe of non-apoptotic cell death and oncogenic-RAS synthetic lethality.
- Skouta, Rachid,Hayano, Miki,Shimada, Kenichi,Stockwell, Brent R.
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scheme or table
p. 5707 - 5713
(2012/10/07)
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- Debenzylation using catalytic hydrogenolysis in trifluoroethanol, and the total synthesis of (-)-raumacline
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N-Debenzylations using catalytic hydrogenolysis often fail to take place unless alcoholic solvents are used, but this can lead to N-alkylation as a side reaction; using trifluoroethanol as the solvent overcomes this problem, and leads to highly reliable hydrogenolyses for a wide range of substrates, including the final deprotection step in our total synthesis of (-)-raumacline.
- Bailey, Patrick D.,Beard, Mark A.,Dang, Hoa P.T.,Phillips, Theresa R.,Price, Richard A.,Whittaker, James H.
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p. 2150 - 2153
(2008/09/20)
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- Synthesis of chiral 3-substituted hexahydropyrroloindoline via intermolecular cyclopropanation
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(Chemical Equation Presented) A new and efficient synthetic route to chiral 3-substituted hexahydropyrroloindoline 18 possessing absolute configurations in accordance with indole alkaloids has been developed from readily available L-tryptophan. The key step relies on the one-pot cascade reaction of oxazolidinone 17 with diazoester, which proceeds through intermolecular cyclopropanation, ring opening, and cyclization.
- Song, Hao,Yang, Jun,Chen, Wei,Qin, Yong
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p. 6011 - 6014
(2007/10/03)
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- 2-Thioindoles as precursors to spiro-fused indolines: Synthesis of (±)-dehaloperophoramidine
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(Chemical Equation Presented) Closing the ring: The cyclization of a 2-thioindole with an electrophilic substituent serves as the key transformation in a synthetic strategy for the generation of indole alkaloids of the perophoramidine and communesin class. DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene, Ms = methanesulfonyl chloride.
- Sabahi, Amir,Novikov, Alexei,Rainier, Jon D.
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p. 4317 - 4320
(2007/10/03)
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- A ring closing metathesis approach to the indole alkaloid mitralactonine
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An efficient utilisation of RCM leading to a convenient synthesis of a pentacyclic indole alkaloid is described.
- Chavan, Subhash P.,Sharma, Pallavi,Sivappa,Kalkote, Uttam R.
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p. 9301 - 9303
(2007/10/03)
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- N-Alkylation of phenethylamine and tryptamine
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A clean and efficient method for the N-alkylation of tryptamine and phenethylamine, employing alcohols as the alkylating agents, has been developed. The reaction proceeds via catalytic electronic activation, involving an iridium catalyst which activates the alcohol by borrowing hydrogen from the substrate, returning it later in the catalytic cycle. Some examples of N-heterocyclisation have been performed employing a diol as the substrate.
- Cami-Kobeci, Gerta,Slatford, Paul A.,Whittlesey, Michael K.,Williams, Jonathan M.J.
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p. 535 - 537
(2007/10/03)
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- Approaches to the synthesis of (+/-)-strychnine via the cobalt-mediated [2 + 2 + 2] cycloaddition: rapid assembly of a classic framework.
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Five synthetic approaches to racemic strychnine (1), with the cobalt-mediated [2 + 2 + 2] cycloaddition of alkynes to indoles as the key step, are described. These include the generation and attempted cyclization of macrocycle 8 and the synthesis of dihydrocarbazoles 15, 22, and 26 and their elaboration to pentacyclic structures via a conjugate addition, dipolar cycloaddition, and propellane-to-spirofused skeletal rearrangement, respectively. Finally, the successful total synthesis of 1 is discussed. The development of a short, highly convergent route (14 steps in the longest linear sequence) is highlighted by the cyclization of enynoylindole 40 with acetylene and the formal intramolecular 1,8-conjugate addition of amine 49 to form pentacycle 50. Numerous attempts toward the formation of the piperidine ring of 1 from vinyl iodide 56 were made and its successful formation via palladium-, nickel-, and radical-mediated processes is described.
- Eichberg,Dorta,Grotjahn,Lamottke,Schmidt,Vollhardt
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p. 9324 - 9337
(2007/10/03)
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- Indole derivatives with antimycobacterial activity
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1,3-Dinitro-2-(indol-3'-yl)-propanes 3 are synthesized by Michael reaction of nitromethane with the indolylnitroethenes 2. - Reaction of the aldehydes 4 and 10 with the benzylamines 12 as well as the reaction of the indolylalkylamines 6a and 9a with the benzaldehydes 11 lead to Schiff bases which are reduced to N-benzyl-(indol-3-ylmethyl)-amines 13 and N-benzyl-(indol-3-ylethyl)-amines 14, respectively; tert amines 16 are synthesized via the formamides 15, amines 18 are prepared according to Mannich. - Inhibitory effects on Mycobacterium tuberculosis H 37 Ra are investigated, a structure-activity relationship is discussed.
- Mahboobi,Grothus,Meindl
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p. 105 - 114
(2007/10/02)
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- Synthesis of Manzamine C, Infractine and 6-Hydroxyinfractine
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Manzamine C (1), a β-carboline alkaloid with antitumor activity isolated from the marine sponge Haliclona sp. was synthesized.The dilithium derivative of 5-hexynoic acid (6) was alkylated with 7 to give after esterification the methyl 10-hydroxy-5-decynoate (8).The tosylate of 8 was converted into the azide 9 which could be selectively hydrogenated with Lindlar palladium catalyst to give the amino ester 10.Saponification of 10 and acylation with (Boc)2O yielded 11, which was converted with pentafluorophenol into 12.Removal of the Boc group in 12 gave an amino ester as intermediate, which cyclized immediately under high dilution conditions to give the lactam 13 in high yield.Reduction of 13 with LiAlH4 produced the macrocyclic amine 4.The β-carboline part of 1 was prepared by condensation of N-benzyltryptamine 14 with the formylacetic acid equivalent 15 to give 16.Dehydrogenation of 16 with Pd-on-carbon catalyst led to the orthoester 17, which could be converted into the methyl ester 5 in high overall yield.The 4-(dimethylamino)pyridine-catalyzed substitution of the methyl ester function in 5 by the amine 4 gave the amide 29.The analogous reaction of 5 with pyrrolidine or with azacyclotridecane yielded 30 and 31.Reduction of these three amides with LiAlH4 produced 1, 2 and 3.The spectroscopic properties of 1 were identical with those of natural manzamine C. - Condensation of 14 or N-benzyl-5-(benzyloxy)tryptamine (19) with aldehyde 18 yielded the products 20 and 21, which could be dehydrogenated to furnish 22 and 23.From these the methyl esters 24 and 25 with properties identical to those of the known β-carboline alkaloids infractine and 6-hydroxyinfractine could be obtained.
- Nowak, Wolfgang,Gerlach, Hans
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p. 153 - 160
(2007/10/02)
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