- Rhodium-Catalyzed Stereoselective Cyclization of 3-Allenylindoles and N-Allenyltryptamines to Functionalized Vinylic Spiroindolenines
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Herein, we report a highly enantio- and diastereoselective rhodium-catalyzed cyclization of N-allenyltryptamines and 3-allenylindoles to 6-membered spirocyclic indolenines. This allylic addition methodology offers the advantage of using a comparably cheap commercially available ligand with low loadings of an affordable rhodium precursor. The products can be converted into functionalized spirooxindoles and spiroindolines, which are regarded as important building blocks for the synthesis of a lot of natural products with biological activities.
- Becker, Antonia,Breit, Bernhard,Grugel, Christian P.
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supporting information
p. 3788 - 3792
(2021/05/29)
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- Catalyst-Controlled Regiodivergence in Rearrangements of Indole-Based Onium Ylides
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We have developed catalyst-controlled regiodivergent rearrangements of onium-ylides derived from indole substrates. Oxonium ylides formed in situ from substituted indoles selectively undergo [2,3]- and [1,2]-rearrangements in the presence of a rhodium and a copper catalyst, respectively. The combined experimental and density functional theory (DFT) computational studies indicate divergent mechanistic pathways involving a metal-free ylide in the rhodium catalyzed reaction favoring [2,3]-rearrangement, and a metal-coordinated ion-pair in the copper catalyzed [1,2]-rearrangement that recombines in the solvent-cage. The application of our methodology was demonstrated in the first total synthesis of the indole alkaloid (±)-sorazolon B, which enabled the stereochemical reassignment of the natural product. Further functional group transformations of the rearrangement products to generate valuable synthetic intermediates were also demonstrated.
- Nair, Vaishnavi N.,Kojasoy, Volga,Laconsay, Croix J.,Kong, Wang Yeuk,Tantillo, Dean J.,Tambar, Uttam K.
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supporting information
p. 9016 - 9025
(2021/06/30)
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- Natural Products for Drug Discovery: Discovery of Gramines as Novel Agents against a Plant Virus
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Plant viral diseases seriously affect crop yield and quality. The natural product gramine (1) and its simple structural analogues 2-35 were synthesized from indoles, amines, and aldehydes in one step. The antiviral effects of these alkaloids were evaluated systematically. Most of these compounds were found to have higher antiviral effects than commercial ribavirin for the first time. Especially compounds 22, 30, and 31 exhibited significantly higher effects than ningnanmycin, thereby emerging as novel antiviral leads for further optimization. The preliminary implementation indicated that these compounds likely inhibit the assembly of tobacco mosaic virus (TMV) by cross-linking TMV capsid protein. Gramine analogues were also found to have broad-spectrum fungicidal effects. Although gramine has been reported to have influence on germination and development of Erysiphe graminis, these compounds displayed no fungicidal effects against Blumeria graminis f. sp. tritici on wheat in our test. Some of these compounds also exhibited certain insecticidal activities.
- Lu, Aidang,Wang, Tienan,Hui, Hao,Wei, Xiaoye,Cui, Weihao,Zhou, Chunlv,Li, Hongyan,Wang, Ziwen,Guo, Jincheng,Ma, Dejun,Wang, Qingmin
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p. 2148 - 2156
(2019/03/08)
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- Rhodium-Catalyzed Enantioselective Cyclization of 3-Allenyl-indoles: Access to Functionalized Tetrahydrocarbazoles
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A highly selective rhodium-catalyzed cyclization of tethered 3-allenylindoles is reported. In a smooth reaction, 1-vinyltetrahydrocarbazoles are obtained in excellent yields and enantioselectivities. Aside from a great functional group tolerance, this method requires neither the Schlenk technique nor the use of anhydrous solvents. Preliminary mechanistic investigations proved that the reaction proceeds via an intermediary formed spiroindolenine which rapidly undergoes an acid-catalyzed stereospecific migration.
- Grugel, Christian P.,Breit, Bernhard
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supporting information
p. 5798 - 5802
(2019/06/08)
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- Rhodium-Catalyzed Diastereo- And Enantioselective Tandem Spirocyclization/Reduction of 3-Allenylindoles: Access to Functionalized Vinylic Spiroindolines
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A highly selective rhodium-catalyzed tandem spirocyclization/reduction of 3-allenylindoles is reported. By employing a Hantzsch ester as reductant, vinylic spiroindolines are obtained in excellent yields as well as diastereo- and enantioselectivity. In addition, the reaction's synthetic utility is highlighted by broad functional group compatibility and exemplified by a gram scale reaction with subsequent assorted transformations.
- Grugel, Christian P.,Breit, Bernhard
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supporting information
p. 9672 - 9676
(2019/12/24)
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- MAP4K4 (HGK) Inhibitors
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The invention provides mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) inhibitors, and pharmaceutically acceptable salts, hydrides and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant diminution of tumor cell growth, cancer or metastasis.
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Paragraph 0133
(2016/08/10)
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- Gramine Derivatives Targeting Ca2+ Channels and Ser/Thr Phosphatases: A New Dual Strategy for the Treatment of Neurodegenerative Diseases
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We describe the synthesis of gramine derivatives and their pharmacological evaluation as multipotent drugs for the treatment of Alzheimer's disease. An innovative multitarget approach is presented, targeting both voltage-gated Ca2+ channels, cl
- Lajarín-Cuesta, Rocío,Nanclares, Carmen,Arranz-Tagarro, Juan-Alberto,González-Lafuente, Laura,Arribas, Raquel L.,Araujo De Brito, Monique,Gandía, Luis,De Los Ríos, Cristóbal
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p. 6265 - 6280
(2016/07/26)
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- A convenient metal-free reagent for the generation and capture of trifluoromethanethiol
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O-Octadecyl-S-trifluorothiolcarbonate is a cheap and storable crystalline source of trifluoromethanethiol that can be prepared in two steps on a multigram scale from trifluoroacetic anhydride and sodium O-octadecyl-dithiocarbonate (xanthate). It reacts directly with gramines or with α-bromoketones and -esters in the presence of KF and pyrrolidine to give the corresponding trifluoromethyl sulfides in generally high yield.
- Li, Shi-Guang,Zard, Samir Z.
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supporting information
p. 5898 - 5901
(2013/12/04)
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- New synthetic approach to paullones and characterization of their SIRT1 inhibitory activity
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A series of 7,12-dihydroindolo[3,2-d][1]benzazepine-6(5H)-ones (paullones) substituted at C9/C10 (Br) and C2 (Me, CF3, CO2Me) have been synthesized by a one-pot Suzuki-Miyaura cross-coupling of an o-aminoarylboronic acid and methyl 2-iodoindoleacetate followed by intramolecular amide formation. Other approaches to the paullone scaffold based on Pd-catalyzed C-H activation were unsuccessful. In vitro enzymatic assay with recombinant human SIRT-1 indicated a strong inhibitory profile for the series, in particular the analogue with a methoxycarbonyl group at C2 and a bromine at C9. These compounds are, in general, inducers of granulocyte differentiation of the U937 acute leukemia cell line and cause a marked increase in pre-G1 of the cell cycle.
- Soto, Sara,Vaz, Esther,Dell'Aversana, Carmela,Alvarez, Rosana,Altucci, Lucia,De Lera, Angel R.
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supporting information; experimental part
p. 2101 - 2112
(2012/04/23)
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- INDOLOPYRIDINES AS INHIBITORS OF THE KINESIN SPINDLE PROTEIN (EG5 )
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Compounds of formula (I), in which R1, R2, R3 and R4 have the meanings indicated in the description, are effective Eg5-inhibiting compounds with anti-proliferative and/or apoptosis inducing activity.
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Page/Page column 80
(2009/04/25)
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- TETRACYCLIC INDOLOPYRIDINES AS EG5 INHIBITORS
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Compounds of a certain formula (I), in which R1, R2, R3 and R4 have the meanings indicated in the description, are effective Eg5-inhibiting compounds with anti-proliferative and/or apoptosis inducing activity.
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Page/Page column 77
(2009/04/25)
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- Enantioselective gold-catalyzed allylic alkylation of indoles with ALcohols: An efficient route to functionalized tetrahydrocarbazoles
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[Chemical equation presented] Breaking the taboo: The direct use of allylic alcohols in catalytic and enantioselective Friedel-Crafts alkylation is described for the first time In the presence of chiral gold complexes. This intramolecular Friedel-Crafts reaction was used to prepare a broad range of functionalized tetrahydrocarbazoles (see scheme; X=Me, F, Br, Cl, OMe; R=Me, Et, tBu; R′=H, Me).
- Bandini, Marco,Eichholzer, Astrid
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supporting information; experimental part
p. 9533 - 9537
(2010/03/24)
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- A practical synthesis of indole-based heterocycles using an amidoaluminum-mediated strategy
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A large number of biologically active compounds consist of an indole scaffolding. Because of this, chemists are continually searching for more efficient means through which to successfully synthesize the required alkaloids. In our recent effort to synthes
- Todd, Robert,Hossain, M. Mahmun
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experimental part
p. 1846 - 1850
(2010/01/16)
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- INDOLOPYRIDINES AS EG5 KINESIN MODULATORS
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Compounds of a certain formula (I), in which R1, R2, R3, R4, R5 and R6 have the meanings indicated in the description, are effective compounds with anti-proliferative and/or apoptosis inducing activity.
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Page/Page column 122
(2008/06/13)
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- INHIBITORS OF ISOPRENYLCYSTEINE CARBOXYL METHYLTRANSFERASE
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The present invention relates, in general, to isoprenylcysteine carboxyl methyltransferase (Icmt) and, in particular, to inhibitors of Icmt and to methods of disease treatment using same.
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Page/Page column 25
(2008/06/13)
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- Substituted indole acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
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This invention provides compounds of the formula: wherein: X is a chemical bond, —CH2— or —C(O)—; R1 is alkyl, cycloalkyl, —CH2-cycloalkyl, pyridinyl, —CH2-pyridinyl, phenyl or benzyl; R2 is H, alkyl, cycloalkyl, —CH2-cycloalkyl, or perfluoroalkyl; R3 is H, halo, alkyl, perfluoroalkyl, alkoxy, cycloalkyl, —CH2-cycloalkyl, —NH2, or —NO2; R4 is optionally substituted phenyl, benzyl, benzyloxy, pyridinyl, or —CH2-pyridinyl, or the salt or ester forms thereof, as well as methods for using the compounds as inhibitors of plasminogen activator inhibitor-1 (PAI-1) and as therapeutic compositions for treating conditions resulting from fibrinolytic disorders such as deep vein thrombosis and coronary heart disease, and pulmonary fibrosis.
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- Synthesis of new melatonin analogues from dimers of azaindole and indole by use of Suzuki homocoupling
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N-{2-[3′-(2-Acetylaminoethyl)-1H,1′H-[5,5′]biindol-3-yl]- and N-{2-[1′-(2-acetylaminoethyl)-1′H-[5, 5′]biindol-1-yl]ethyl}acetamide (2,3) and their analogues in 7-azaindole series (4,5) were synthesized by palladium catalysed reaction starting from indole or 7-azaindole using [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium, as catalyst.
- Guillard, Jerome,Larraya, Carlos,Viaud-Massuard, Marie-Claude
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p. 865 - 877
(2007/10/03)
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- Bromoderivatives of gramines. Preparation and pharmacological properties
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Bromination of gramine (I), 1-methylgramine (IX), 2-methylgramine (IV) and 1,2-dimethylgramine (XV) with different mole ratios of bromine to substrate was investigated; it was seen that the 5- and 6-position are the normal sites of bromination and 1-methylgramines (IX) and (XV) give better yields of bromoderivatives.Among the compounds submitted the pharmacological screening, 2,6-dibromo-1-methylgramine hydrobromide (Xa) and especially 6-bromo-2-methylgramine (V) showed a clear antiserotoninic antiinflammatory and analgesic activity.Furthermore gramine (V) showed a good anti prostaglandin synthetase activity in vitro.Key-words: Bromogramines. - Antiserotonic activity. - Antiinflammatory activity.
- Franzone, Jose Sebastian,Cirillo, Rocco,Cravanzola, Carlo
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p. 261 - 268
(2007/10/02)
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- 3-INDOLYL-TERTIARY BUTYLAMINOPROPANOLS
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1-Phenoxy-3-(3-indolyl)-tert.-butyl!amino-2-propanols and related 1-aryloxy compounds are antihypertensive agents having vasodilator and adrenergic β-receptor blocking action. Preferred compounds bear an ortho-substituent in the phenoxy group, and most preferably the cyano group.
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