Reactions of 3-vinylindole derivatives with dienophiles

Reactions of 3-(1-cyclohexenyl)-1,2-dimethylindole (1a) and the 1,2-dihydrocarbazole 1b with some carbo- and heterodienophiles are described. Thus, compound 1a reacts to give ene, Michael-type, and Diels-Alder adducts, depending on the dienophile and reaction conditions. The 3-vinylindole 1b reacts with 4-phenyl-1,2,4-triazoline-3,5-dione or N-phenylmaleimide in a dehydrogenative reaction to yield the fully aromatized carbazole 8.

First Reactions of 2,2′-Bisindolyls with Electrophilic Azo Compounds and Diethyl Mesoxalate

Conformations and some electronic properties of the 2,2′-bisindolyls 6 were calculated for the prediction of probable Diels-Alder reactivity, in analogy to previous work on 2-vinylindoles. First reactions with dienophiles revealed that compounds 6 did not participate in [4 + 2]cycloadditions but rather underwent simple electrophilic substitutions at the enamine function with, above all, some heterodienophiles. Erste Reaktionen von 2,2′-Bisindolylen mit elektrophilen Azoverbindungen und Diethylmesoxalat Zur Vorhersage moglicher Diels-Alder-Reaktionen an 2,2′-Bisindolylen 6 werden Berechnungen zur Konformation und uber elektronische Eigenschaften durchgefuhrt. Die erstmals durchgefuhrten Reak…

Pyrido[4,3-b]carbazole als neue Cytostatika Entwicklung, Chemie und klinische Anwendung

Das Carbazolalkaloid Ellipticin (aus Apocynaceen) ist aufgrund seines vollig ebenen Baus, seiner funktionellen Gruppen und seiner Molekulgrose befahigt zur DNA-Intercalation.

Synthesis and biological evaluation of structural variants of carbazoquinocin C

Some new structural variants of the alkaloid carbazoquinocin C were synthesized in a few steps with good to excellent yields. The key step comprises a cyclisation reaction of appropriate 2-vinylindoles with oxalyl chloride. The carbazole-3,4-quinones are able to trap oxygen-centred radicals. In some biological/biochemical assays some of these compounds exhibit extraordinary results including inhibition of cyclooxygenase-1 and 5-lipoxygenase in the μM-range. Moreover some of the carbazoquinocin C-variants inhibit significant oxidative damage of cellular DNA in nM-range.

ChemInform Abstract: Diels-Alder Reactions of in situ Generated N-Benzoylindolo-2,3- quinodimethane with Carbodienophiles.

The indolo-2,3-quinodimethane (5), generated from 2,3-bis(bromomethyl)indole (4), was trapped with unsymmetrical carbodienophiles or N, N′-p-phenylenedimaleimide to furnish the 1,2,3,4-tetrahydrocarbazoles (6–9). [4 + 2]-Cycloaddition of 5 with tetracyanoethylene gave rise to the tetracyanocarbazole (10) and a subsequent product 11a or 11b. The Diels-Alder reaction of 5 with divinyl sulfone was regiospecific within the detection limits of HPLC analysis. Similarly, the reaction of 5 with N, N′-p-phenylenedimaleimide yielded solely the stereoisomer 9.

Wittig-Olefinierung zu neuen donor- und akzeptor-substituierten 3-Vinylindolen: Optimierte Syntheseverfahren

The optimized Wittig reaction of selectively functionalized 3-acylindoles yield new, and for Diels-Alder reactions highly reactive donor- and acceptor substituted 3-vinylindoles, respectively.

Zur protonenkatalysierten Xanthenylierung von Tryptamin, Nω-Acetyltryptamin und Gramin: Ein Beitrag zur Konstitutionsaufklärung in der Indol-Analytik

Selektive Synthesen zu 1?-aryl-, 1?-hetaryl-und 1?-alkylsubstituierten 3-Vinylindolen

Selective methods for deriving 1′-aryl-, 1′-indolyl-, 1′-pyrrolyl- and 1′-methyl-substituted 3-vinylindoles2 are described. In all cases the precursors were 3-acylindoles. The new compounds are synthetically useful synthons for annelation of the indole skeleton.

The Reactions of Electron-Rich Heterocycles with Derivatives of Orthocarboxylic Acids; VIII. Proton Acid-Catalyzed Acylation of Indoles by 2-Alkoxy-1,3-dioxolanes

In acid-catalyzed reactions with 3-unsubstituted indoles 1, 2-alkoxy-1,3-dioxolanes 2a-c behave as acyl equivalents. Depending on the substitution patterns of the reaction partners, the 1,3-dioxolanium ions 3a-c, generated in situ from the cyclic ortho esters by the action of sulfosalicylic acid, react to form tris-(3-indolyl)alkanes 6 and 9, bis-(3-indolyl)ethenes 7, or 3-benzoylindoles 8. Analogous reactivity was observed with related acyclic ortho esters. Reaktionen elektronenreicher Heterocyclen mit Orthocarbonsaure-Derivaten; VIII. Protonsaurekatalysierte Acylierung von Indolen mit 2-Alkoxy-1,3-dioxolanen 2-Alkoxy-1,3-dioxolane 2a-c reagieren als Acylaquivalente mit 3-unsubstituierten …

Proton Acid-Catalysed Transformations of Estrogen Derivatives: New Results and Some Mechanistic Aspects of theKober Colour Reaction

The 3-O-methylated estrogen derivatives 1a-d and α-estradiol (1e) underwent sulfuric acid-catalysed transformations to furnish the steroids 2–6. The processes involved in the reaction sequence are regioselective sulfonation and, above all, the Wagner-Meerwein rearrangement of the methyl group at C-13. With the objective of obtaining further information on the course of the Kober colour reaction of estrogens, some UV/VIS and ESR spectroscopic investigations were also carried out. Protonenkatalysierte Transformationen von Estrogen-Derivaten: Neue Ergebnisse und einige mechanistische Aspekte der Kober-Farbreaktion Die O-methylierten Estrogenderivate 1a-d und α-Estradiol (1e) reagieren in Schwe…

ChemInform Abstract: Reactions of Pyrano(3,4-b)indol-3-ones with Dienophiles: Consecutive (4 + 2) Cycloaddition/Cycloreversion/1,2 Elimination.

Methylpyrano[3,4-b]indol-3-ones 1 react with selected dienophiles (as acetylene equivalents) in a consecutive Diels-Alder/cycloreversion/1,2 elimination reaction sequence to furnish the 1-methyl- and 1,4-dimethylcarbazoles 4.

The mechanism of formation of 3H,9H-Pyrano[3,4-b]indol-3-ones from 3-indolalkanoic acids

The mechanism of the formation of 1-methyl-3H,9H-pyrano[3,4-b]indol-3-one (4) from the corresponding 3-indolacetic acid 1 is discussed. The suggested mechanism is substantiated by the isolation of a stable intermediate 2 and its transformations in the presence of acetic anhydride and/or Lewis acids.

N-benzoylindole-2,3-quinodimethane: Diels-Alder reactivity and synthetic applications for [b]annellated indoles

Abstract The Diels-Alder reactivity of in situ generated N -benzoylindole-2,3-quinodimethane has been expanded considerably to include reactions with carbon- and hetero-dienophiles which furnish a variety of [ b ]annellated indoles as well as functionalized and annellated carbazoles. The frontier molecular orbital theory was found to be a useful model for the prediction of the experimental results under consideration of reactivity aspects.

ChemInform Abstract: Recent Advances in the Synthesis of Carbazoles and Anellated Indoles with Antitumor Activity: DNA-Binding Ligands and Protein Kinase C Inhibitors

ChemInform Abstract: Novel Bis(tetrahydropyrrolo[3,4-b]carbazoles) Linked with Aliphatic Chains: Synthesis and Structural Aspects.

ChemInform Abstract: New Reactions of Amino-Functionalized 3-Vinyl-1H-indoles and Tetrahydropyridin-4-yl Analogues with Dienophiles.

Reactions of 3-[2-(morpholin-4-yl)vinyl]-1H-indole (1), the 1,2-dihydro-9H-carbazole 2, as well as the 3-(tetrahydropyridin-4-yl)-1H-indoles 3a and 3b with some carbo- and heterodienophiles are described. The scope and limitations of the synthetic utility of these amino- (or homoamino)-functionalized 3-vinyl-1H-indoles are reported and some MO calculations for the qualitative prediction of their reactivities are presented. The reactions gave rise to substitution products, redox products, Diels-Alder adducts, ene adducts, and Michael-type adducts (Schemes 2 and 3).

ChemInform Abstract: New Electrophilic Reactions of 2,2′-Bisindolyls with Acid Chlorides and Carbodienophiles.

Some new acylation and cyclization reactions of 2,2′-bisindolyls 1, 2 are described. The product patterns constitute acyl derivatives 3, 4, 5 and an aldehyde 7, indolo[2,3-a]carbazoles 6, 14, 17, 19, 20 and cyclopentadiindoles 22 and 24. In the reaction with aryne or diazotated anthranilic acid, a 3-benzoylindole derivative 9 and phenylindolyl azo dye 10 are formed. N-methylmaleimide reacts with 2,2′-bisindolyl 2 via Michael type addition, dehydrogenation and cyclization to several functionalized or anellated indole derivatives 11, 12, 13 and 14, respectively.

[a]-Anellated carbazoles with antitumor activity: Synthesis and cytotoxicity

The cycloadducts3,5, and7, readily available from methoxy-substituted 3-vinylindoles1 and2, were dehydrogenated withDDQ to the coplanar [a]-anellated carbazoles4,6, and8. Compound4a, also characterized by X-ray structural analysis, shows significant cytotoxicity against K562 und RXF393 human tumor cell lines.

Synthesis of new bis(tetrahydropyrrolo[3,4-b]carbazoles) with a functionalized diaryl spacer

Some new bis(tetrahydropyrrolo[3,4-b]carbazoles) were synthesized by Diels–Alder reactions of in-situ generated indole-2,3-quinodimethanes with a variety of bismaleimides as dienophiles and also by reaction of dianilines with a succinic acid anhydride group incorporated into a biscarbazole. In a special reaction a spermine linker was introduced. The new biscarbazoles represent potential DNA ligands for the development of new antitumor active drugs.

ChemInform Abstract: Antitumor Drug Design: DNA-Binding Ligands, Which Inhibit the Topoisomerase I

ChemInform Abstract: New Studies and a Reinvestigation on (4 + 2) Cycloadditions of (-)- Thebaine: Asymmetrical Diels-Alder Reactions with a Conformationally Fixed Chiral Diene.

Some novel Diels-Alder reactions of the opium alkaloid (−)-thebaine (1) as an electron-rich diene and a reinvestigation of its reactions with cyclic and acyclic dienophiles are described. The π-facial selectivity has been studied on the basis of structural analyses of the cycloadducts. Some related results on [4 + 2] cycloaddition reactions of 1-methoxy-1,3-cyclohexadiene (11) are also reported.

ChemInform Abstract: Photochemical Electrocyclization of 3-Vinylindoles (VIII) to Pyrido[2,3-a]- (IX), Pyrido[4,3-a]- (X) and Thieno[2,3-a]-carbazoles (XIII): Design, Synthesis, DNA Binding and Antitumor Cell Cytotoxicity.

New potential DNA intercalators of the carbazole series from indole-2,3-quinodimethanes: Synthesis, crystal structure, and molecular modeling with a watson-crick mini-helix

1-Alkylpyrano[3,4-b]indol-3-ones3 react via a Diels-Alder step with an aryne or N-phenylmaleimide to furnish the new [b]annellated carbazoles4–10 in a one-pot process. In an analogous procedure, the in situ generated N-benzoylindole-2,3-quinodimethane (13) reacted with quinones to furnish the dioxocarbazoles14–16. Compounds4–8 and14–16 with a coplanar skeleton are members of a class of potential DNA intercalators, as has been shown for5 and8 by X-ray structural analysis. On the basis of the geometries determined by X-ray crystallography, the intercalative binding of these molecules with a Watson-Crick mini-helix was predicted by molecular modeling methods.

Reaktivitäut und reaktionswege von methylsubstituierten bisindolylcarbenium-ionen

Methyl substituted bisindolylcarbenium ions 1 react with some O- and C-nucleophiles regioselectively. The cations 1b, 1c yield with hydroxide ions the tetraindolyldimethyl ether 4 and with methoxide ions the bisin-dolylmethoxymethanes 5. Compounds 1a, 1b, 1c react with several methylindoles to isomeric bis- and trisin-dolylmethanes. An electrophilic reactivity order of cations 1 can be derived supporting on the experimental results.

Photochemical electrocyclisation of 3-vinylindoles to pyrido[2,3-a]-, pyrido[4,3-a]- and thieno[2,3-a]-carbazoles: Design, synthesis, DNA binding and antitumor cell cytotoxicity

In the context of the design and synthesis of DNA ligands, some new hetarene annelated carbazoles were synthesized. As lead structure the intercalating tetracyclic systems pyrido[2,3-a]- and pyrido[4,3-a]-carbazoles and in one case a thieno[2,3-a]-carbazole were taken into account. A dialkyl amino amidic chain was introduced to the planar chromophoric system with the intent to generate minor groove binding properties. The cytotoxicity of some compounds was examined by the NCI antitumor screening. Furthermore, biophysical as well as biochemical studies were performed in order to get some information about the DNA-binding properties and inhibition of DNA related functional enzymes of this new…

Thermal 1,6-Electrocyclization Reactions of Acceptor-Substituted 2,3-Divinyl-1H-indoles Yielding Functionalized Carbazoles

Three new synthetic procedures for and thermal 1,6-electrocyclizations of acceptor-substituted 2,3-divinyl-1H-indoles leading to functionalizing carbazoles are described. The scope and limitations as well as some mechanistic aspects of the methodologies are discussed. The key strategies employed include Pd(II)-catalyzed coupling and Wittig procedures.

Diels-Alder-Reaktionen von Vinylindolen mit Arin und 1,4-Benzochinonen: Neue potentielle DNA-Interkalatoren

Diels-Alder reactions of 2- and 3-vinylindoles with aryne, 1,4-benzo- and 1,4-naphtho-quinone lead to new six-ring annellated carbazoles. Molecular modeling studies predict that the compounds with coplanar framework are able to intercalate with the B-DNA.

ChemInform Abstract: First Reactions of Dialkoxycarbenium Tetrafluoroborates with Pyrroles, 5H-Dibenz(b,f)azepines, and Electron-Rich Arenes.

Pyrrole (2a) and 2,5-dimethylpyrrole (2b) react with the dialkoxycarbenium tetrafluoroborates 1a-1c under kinetic control to yield the corresponding acylpyrrole derivatives. 5H-Dibenz[b,f]azepine (9a) and the 10,11-dihydro derivative 9b react only with the most electrophilic of the series of electrophiles tested, namely, diethoxycarbenium tetrafluoroborate (1a), to furnish the corresponding formyl derivatives. Similarly, in arene chemistry, the highly electron-rich N,N-dimethylaniline (13a) and 1,3,5-trimethoxybenzene (13b) are formylated by reaction with 1a.

Synthesis and Biological Evaluation of Structural Variants of Carbazoquinocin C.

First transformations of pyrano[3,4-b]indol-3-ones to salvadoricine and 2,3-diacylindoles

The readily available methylated pyrano[3,4-b]indol-3-ones 1a and 1b were hydrolyzed to furnish the 2-acetylindol-3-alkanoic acids 2 and 4. Compound 2 was easily transformed selectively to 2-acetyl-3-methylindole (3, salvadoricine). Substrate 1b reacts with molecular oxygen from the air only in the presence of a catalyst to give 2,3-diacetylindole (5) while 1a reacts with nitrosobenzene via a proposed Diels-Alder step to yield 2-acetylindole-3-carbaldehyde (6). The latter product can also be obtained in low yield from the reaction of 1a with molecular oxygen from the air.

Diels-alder reactions of methyl- and π-acceptor-substituted 2-vinylindoles with dimethyl acetylenedicarboxylate and tetracyanoethylene: Novel functionalized carbazoles

The Diels-Alder reactions of the 2-vinylindoles 1a-1d, which are now readily accessible, with dimethyl acetylenedicarboxylate and tetracyanoethylene give rise to the novel 1,2-dihydro- and 1,2,3,4-tetrahydrocarbazoles 2, 4, and 5 as well as the fully aromatized carbazoles 3. With regard to the product spectrum, the mechanistic rationale comprises a Diels-Alder step, formal 1,3-hydrogen shift, ene reaction, and dehydrogenation. Conformational aspects of the 1,2-dihydrocarbazoles 2b and 2c are also discussed.

Reaktionen von elektronenreichen Heterocyclen mit Orthocarbonsäure-Derivaten, 10. Formylierungs- und Alkylierungsreaktionen von Carbazolen mit ambidenten Dialkoxycarbenium-tetrafluoroboraten

Carbazole werden durch Diethoxycarbenium-tetrafluoroborat mit hoher Regioselektivitat formyliert, wahrend die thermodynamisch stabileren Diethoxymethylcarbenium- und Trimethoxycarbenium-Ionen infolge ausgepragter ambidenter Elektrophilie Carbazole bevorzugt alkylieren. Reactions of Electron-Rich Heterocycles with Orthocarboxylic Acid Derivatives, 10. – Formylation and Alkylation of Carbazoles with Ambident Dialkoxycarbenium Tetrafluoroborates Carbazole and some derivatives were formylated regioselectively with diethoxycarbenium tetrafluoroborate. The thermodynamically more stable diethoxymethylcarbenium and trimethoxycarbenium ions exhibit ambident electrophilic reactivity as predominant al…

ChemInform Abstract: A New and Effective Method to Carbazoquinocin C and Related Carbazole-3,4-quinones as Biological Antioxidants: Key Reactions of 2-Vinylindoles with Oxalyl Chloride.

ChemInform Abstract: Carbazole Synthesis via an in situ Trapping Strategy with Indolyl Enol Ethers.

Indolyl enol ethers, generated from the alkoxy(indolyl)carbenium tetra- fluoroborates (1) by treatment with sodium hydride, can be trapped with dimethyl acetylenedicarboxylate or N-phenylmaleimide to furnish the se- lectively functionalized carbazoles (3), (4), (5), (9), (10), and (13). In addition, the biaryl derivatives (6) and (11) are produced by a ring- opening reaction of the primarily formed Diels-Alder adduct. In the case of the biaryl derivative (6), an X-ray crystal structure analysis yields valuable information on constitutions and configurations in the biaryl series. The phenomenon of atropisomerism is discussed for this compound

Reaktionen von elektronenreichen Heterocyclen mit Orthocarbonsäure-Derivaten, 9. Acylierungsreaktionen von Indol und Methylindolen mit Dialkoxycarbenium-tetrafluoroboraten

Indol und einige Methylderivate 1 lassen sich unter milden Bedingungen mit den Dialkoxycarbenium-tetrafluoroboraten 2 in meist guten Ausbeuten regioselektive acylieren. Mit dem Formylkation-Aquivalent 2a′ werden mit uberschussigem 1 auch die Bisindolycarbenium-tetrafluoroborate 13a – d erhalten. Reactions of Electron-rich Heterocycles with Orthocarboxylic Acid Derivatives, 9. – Acylation of Indole and Methylindoles with Dialkoxycarbenium Tetrafluoroborates Indole and some methylindoles 1 were acylated regioselectively with dialkoxycarbenium tetrafluoroborates 2 under mild conditions. The formyl cation equivalent 2a′ reacts with excess of indoles 1 to give the bisindolylcarbenium tetrafluoro…

ChemInform Abstract: New Indolocarbazoles as Antitumor Active Compounds: Evaluation of the Target by Experimental and Theoretical Studies.

Diels-Alder reactions of 1-phenylpyrano[3,4-b]indol-3-ones with alkynes: New functionalized carbazoles

3-Indolylalkanoic acids 2 react with benzoic acid anhydride under catalysis of Et2O - ZnCl2 and mild conditions to furnish the 1-phenyl-substituted pyrano[3,4-b]indol-3-ones 1c, 1d, and 3a, 3b. Products 1c, 1d, and 3b may be converted into the novel functionalized carbazoles 4 and 5 by reaction with acceptor-substituted alkynes.

First synthesis of chiral 3-vinylindoles as 4π-components for diels-alder reactions

The first syntheses of chiral 3- and 2-vinylindoles bearing sulfoxide or (-)-menthyloxy functional groups at the β-vinyl positions by way of procedures based on the Horner-Wadsworth-Emmons and Wittig reactions, respectively, are described. Some Diels-Alder reactions demonstrating the 4π-reactivity of these compounds are reported.

3-Vinyl-1H-indoles: A conformational study, electronic aspects and reactivity predictions forDiels-Alder reactions

On the basis of X-ray geometries, a theoretical conformational study of some 3-vinyl-1H-indoles was performed with quantum chemistry and molecular mechanics programs. Charge, frontier orbitals, and the molecular electrostatic potential derived from quantum chemistry calculations of 3-vinyl-1H-indoles are reliable reactivity parameters to predict the outcome of theDiels-Alder reaction.

ChemInform Abstract: Diels-Alder Reactions of 1-Phenylpyrano(3,4-b)indol-3-ones with Alkynes: New Functionalized Carbazoles.

3-Indolylalkanoic acids 2 react with benzoic acid anhydride under catalysis of Et2O - ZnCl2 and mild conditions to furnish the 1-phenyl-substituted pyrano[3,4-b]indol-3-ones 1c, 1d, and 3a, 3b. Products 1c, 1d, and 3b may be converted into the novel functionalized carbazoles 4 and 5 by reaction with acceptor-substituted alkynes.

1,6-π-Electrocyclization of 3-Vinyl-FunctionalizedN,N-Dimethyl-2,2′-Bisindolyl: Some analysis of the educt transformation process

The thermally and photochemically induced 1,6-π-electrocyclization reaction of 3-vinyl-functionalized N, N'-dimethyl-2,2′-bisindolyls 4 has been analysed and some reactivity aspects are presented. On the basis of time dependent 1H nmr and uv spectroscopic measurements the educt transformations can be observed in detail. Some results of the isomerization process of the educts are also given.

Regioselective proton-catalyzed diarylmethylation of indoles with 9H-xanthydrol, dibenzosuberenol, and bis[4-dimethylaminophenyl]methanol

3-Isopropylindole (4) is xanthenylated both at N-1 (stereocontrolled major reaction), C-2, and on the phenyl nucleus of the indole skeleton by xanthydrol (1). Other carbinols such as dibenzosuberenol (2) and bis[4-dimethylaminophenyl]methanol (3) with lower electrophilic SN1 activities than 1 do not react with 4 but do react very selectively with simple methylindoles to form diarylmethylated derivatives.

Interkalationsmodelle von Cytostatika mit der B-DNA

Functionalization with silyl enol ethers, VI Zinc chloride mediated alkoxyalkylation of O-methyl-O-trimethylsilyl) keten acetals with 2-alkoxy-1,3-dioxolanes

O-Methyl-O-(trimethylsilyl) keten acetals2 were regioselectively alkoxyalkylated by 2-alkoxy-1,3-dioxolanes1 in the presence of zinc chloride. This method represents a good way for synthesis of α-protected β-keto carbonic esters4.

Mechanismus und Reaktionswege der Xanthenylierung an ambidenten nukleophilen Arzneistoffen

Am Beispiel der ambidenten nukleophilen Arzneistoffe 4-Aminobenzolsulfonamid (3), Indometacin (7) und Phenylbutazon (10) werden Aralkylierungen mit dem SN1-aktiven Reagens Xanthydrol (1) vorgestellt. Mechanism and Reaction Path of the Xanthenylation of Ambident Nucleophilic Drugs The aralkylation of ambident nucleophilic drugs, e.g. 4-aminobenzenesulfonamide (3), indometacine (7) and phenylbutazone (10), with SN1-active xanthydrol (1) is described.

New Reactions of Amino-Functionalized 3-Vinyl-1H-indoles and Tetrahydropyridin-4-yl Analogues with Dienophiles

Reactions of 3-[2-(morpholin-4-yl)vinyl]-1H-indole (1), the 1,2-dihydro-9H-carbazole 2, as well as the 3-(tetrahydropyridin-4-yl)-1H-indoles 3a and 3b with some carbo- and heterodienophiles are described. The scope and limitations of the synthetic utility of these amino- (or homoamino)-functionalized 3-vinyl-1H-indoles are reported and some MO calculations for the qualitative prediction of their reactivities are presented. The reactions gave rise to substitution products, redox products, Diels-Alder adducts, ene adducts, and Michael-type adducts (Schemes 2 and 3).

ChemInform Abstract: (4 + 2) Cycloaddition of Indole Derivatives with Bismaleimides: A Route to New Biscarbazoles.

ChemInform Abstract: First Electrophilic Substitutions of 3-Substituted Indoles with Diethoxycarbenium Tetrafluoroborate: Functionalized Indole Derivatives.

The indoles 2a-2c react with diethoxycarbenium tetrafluoroborate (1) to furnish the indolecarbaldehydes 3a-3d. In the thermodynamically controlled reaction of 3-methylindole (2a) with 1 the tris(indolyl)methane 4 and diskatole (5), are formed in addition. The limitations of these reactions are discussed and evidence is presented for a C-3-ipso-attack and a Wagner-Meerwein rearrangement, respectively, leading to the formation of 3b or 3d. Erste elektrophile Substitution von 3-substituierten Indolen mit Diethoxycarbenium-Tetrafluoroborat: Funktionalisierte Indol-Derivate Die Indole 2a-2c reagieren mit dem per se synthetisierten Diethoxycarbenium-Tetrafluoroborat (1) zu den Indolcarbaldehyden …

ChemInform Abstract: Synthesis of New Bis(tetrahydropyrrolo[3,4-b]carbazoles) with a Functionalized Diaryl Spacer.

Some new bis(tetrahydropyrrolo[3,4-b]carbazoles) were synthesized by Diels–Alder reactions of in-situ generated indole-2,3-quinodimethanes with a variety of bismaleimides as dienophiles and also by reaction of dianilines with a succinic acid anhydride group incorporated into a biscarbazole. In a special reaction a spermine linker was introduced. The new biscarbazoles represent potential DNA ligands for the development of new antitumor active drugs.

ChemInform Abstract: Diels-Alder Reactions of Methyl- and π-Acceptor-Substituted 2- Vinylindoles with Dimethyl Acetylenedicarboxylate and Tetracyanoethylene: Novel Functionalized Carbazoles.

The Diels-Alder reactions of the 2-vinylindoles 1a-1d, which are now readily accessible, with dimethyl acetylenedicarboxylate and tetracyanoethylene give rise to the novel 1,2-dihydro- and 1,2,3,4-tetrahydrocarbazoles 2, 4, and 5 as well as the fully aromatized carbazoles 3. With regard to the product spectrum, the mechanistic rationale comprises a Diels-Alder step, formal 1,3-hydrogen shift, ene reaction, and dehydrogenation. Conformational aspects of the 1,2-dihydrocarbazoles 2b and 2c are also discussed.

ChemInform Abstract: Synthetic and Mechanistic Aspects of the Course of the Color Reaction of Iminodibenzyl with Aryl- or Hetaryl-aldehydes: An Access to New Hetaryl-/Aryl-methanes and 4,5-Diamino-cyclopentenones.

Cycloadditions of vinylindoles with chiral carbodienophiles: the first asymmetric Diels-Alder reactions in the vinylhetarane series

Abstract The first asymmetric Diels-Alder reactions of some 3- and 2-vinylindoles with (N-propenoyl)bornane-10,2-sultam are described. With one exception, the experimental results are indicative of a high π-facial diastereoselectivity. Following a related procedure, 3-vinylindoles were also allowed to react with a racemic bis(naphthylsulfonyl)-dienophile to furnish tetrahydrocarbazoles with endo-diastereoselectivity.

Pericyclische Schlüsselreaktionen in biologischen Systemen und biomimetische Synthesen – eine Übersicht –

Diels-Alder Reactions ofin situ generated N-benzoylindolo-2,3-quinodimethane with carbodienophiles

The indolo-2,3-quinodimethane (5), generated from 2,3-bis(bromomethyl)indole (4), was trapped with unsymmetrical carbodienophiles or N, N′-p-phenylenedimaleimide to furnish the 1,2,3,4-tetrahydrocarbazoles (6–9). [4 + 2]-Cycloaddition of 5 with tetracyanoethylene gave rise to the tetracyanocarbazole (10) and a subsequent product 11a or 11b. The Diels-Alder reaction of 5 with divinyl sulfone was regiospecific within the detection limits of HPLC analysis. Similarly, the reaction of 5 with N, N′-p-phenylenedimaleimide yielded solely the stereoisomer 9.

Novel bis(tetrahydropyrrolo[3,4-b]carbazoles) linked with aliphatic chains: synthesis and structural aspects

Syntheses of novel bis(tetrahydropyrrolo[3,4-b]carbazoles) by a [4+2]cycloaddition reaction are described. By variation of dienophiles bis(tetrahydropyrrolo[3,4-b]carbazoles) of varying aliphatic spacer length could be obtained in high yields. These conformationally highly flexible molecules represent an interesting class of compounds, believed to have an affinity towards DNA, as potential DNA ligands.

Neue Diels-Alder-Reaktionen von 1-Methylpyrano[3,4-b]indol-3(9H)-on mit cyclischen CC-Dienophilen: ein einfacher Zugang zu [b]anellierten Carbazol-Derivaten

1-Methylpyrano[3,4-b]indol-3(9H)-on (1) reagiert als synthetisches Aquivalent von Indolo-2,3-chinodimethan mit Arin, p-Benzochinon und p-Naphthochinon zu neuen [b]anellierten Carbazol-Derivaten. Durch das Reaktionsmedium bedingt lassen sich bei der Cycloaddition von 1 mit Arin zugleich auch mononitrierte Carbazole isolieren. New Diels-Alder Reactions of 1-Methylpyrano[3,4-b]indol-3(9H)-one with Cyclic CC-Dienophiles: A Simple Way to [b]Annulated Carbazole Derivatives. 1-Methylpyrano[3,4-b]indol-3-(9H)-one (1) reacts as synthetic equivalent of indolo-2,3-quinodimethane with benzyne, p-benzoquinone, and p-naphthoquinone to give new [b]annulated carbazole derivatives. In the Diels-Alder reacti…

ChemInform Abstract: (a)-Anellated Carbazoles with Antitumor Activity: Synthesis and Cytotoxicity.

The cycloadducts3,5, and7, readily available from methoxy-substituted 3-vinylindoles1 and2, were dehydrogenated withDDQ to the coplanar [a]-anellated carbazoles4,6, and8. Compound4a, also characterized by X-ray structural analysis, shows significant cytotoxicity against K562 und RXF393 human tumor cell lines.

Molecular modeling of intercalation complexes of antitumor active 9-aminoacridine and a [d, e]-anellated isoquinoline derivative with base paired deoxytetranucleotides

Intercalators are molecules capable of sliding between DNA base pairs without breaking up the hydrogen bonds between the DNA bases. On the basis of molecular mechanics calculations structural, models of B-DNA tetranucleotide intercalation complexes of some cytostatic active 9-aminoacridines and of a [d, e]-anellated isoquinoline derivative are presented. The drug complexes are stabilized by energetically favouredvan der Waals interactions and by selective hydrogen bonds between the side chains of the drugs and the DNA bases. Semiempirical quantum chemistry calculations revealed that the chromophoric system of the intercalators is able to form π,π-charge-transfer interactions with the purine…

Preparation and chemistry of ortho acids, ortho esters and ortho amides

Electrophilic substitution and cyclization of 2,2′-bis(N-methylindolyl): A simple access to potential protein kinase C inhibitor

A strategy is described for the synthesis of functionalized and cyclized 2,2′-bisindolyl derivatives related to several basic systems of natural products. The starting 2,2′-bis(N-methylindolyl) (8) reacts with a variety of electrophiles and electrophilic dienophiles to furnish the novel, functionalized and cyclized bisindolyl derivatives 9–16. In addition, some reactivity and structural aspects are discussed; an X-ray crystallographic analysis of the 2,2′-bisindolyl 8 provided valuable information for the conformational analyses.

Reaktion von elektronenreichen Heterocyclen mit Orthocarbonsäure-Derivaten, 12. Formylierung von Vinylindolen mit Diethoxycarbenium-tetrafluoroborat

Reactions of Electron-Rich Heterocycles with Orthocarboxylic Acid Derivatives, 12. – Formylation of Vinylindoles with Diethoxycarbenium Tetrafluoroborate 2- and 3-vinylindoles 1, 3 are formylated with diethoxycarbenium tetrafluoroborate regioselectively. The significant selectivity and reactivity of formylation of diethoxycarbenium ion in comparison with other thermodynamically more stable dialkoxycarbenium ions are compatible with the known results of hetaryl functionalisation with orthocarboxylic acid derivatives.

Zur Reaktion von Indolen mit 1,3-Dithiolenium-Ionen: ein einfacher Zugang zu 3-(1,3-Dithiolan-2-yl)indolen

Reaction of Indoles with 1,3-Dithiolenium Ions: a Simple Access to 3-(1,3-Dithiolan-2-yl)indoles 3-Unsubstituted indoles 1 react regioselectively with 2-methyl- and 2-phenyl-1,3-dithiolenium ions 2 under mild conditions to give the 3-(1,3-dithiolan-2-yl)indoles 4 as protected 3-acylindoles.

ChemInform Abstract: First Reactions of 2,2′-Bisindolyls with Electrophilic Azo Compounds and Diethyl Mesoxalate.

Conformations and some electronic properties of the 2,2′-bisindolyls 6 were calculated for the prediction of probable Diels-Alder reactivity, in analogy to previous work on 2-vinylindoles. First reactions with dienophiles revealed that compounds 6 did not participate in [4 + 2]cycloadditions but rather underwent simple electrophilic substitutions at the enamine function with, above all, some heterodienophiles. Erste Reaktionen von 2,2′-Bisindolylen mit elektrophilen Azoverbindungen und Diethylmesoxalat Zur Vorhersage moglicher Diels-Alder-Reaktionen an 2,2′-Bisindolylen 6 werden Berechnungen zur Konformation und uber elektronische Eigenschaften durchgefuhrt. Die erstmals durchgefuhrten Reak…

A new access to 2′-amino-substituted vinylindoles as donor-activated heterocyclic dienes and their first diels-alder reactions

Abstract Reactions of the 3-acylindoles 5, 10 , and 15 with α-amino-α′-diphenylphosphinoyl-substituted carbanions gave rise to the 2′-amino-substituted 3− and 2-vinylindoles 7, 12 , and 17 by way of the isolable carbinols 6 , 11 , and 16 . The heterocyclic dienes 7 , 12 , and 17 readily underwent Diels-Alder reactions with N -phenylmaleimide.

ChemInform Abstract: Regioselective Proton-Catalyzed Diarylmethylation of Indoles with 9H-Xanthydrol, Dibenzosuberenol, and Bis(4-dimethylaminophenyl)methanol.

3-Isopropylindole (4) is xanthenylated both at N-1 (stereocontrolled major reaction), C-2, and on the phenyl nucleus of the indole skeleton by xanthydrol (1). Other carbinols such as dibenzosuberenol (2) and bis[4-dimethylaminophenyl]methanol (3) with lower electrophilic SN1 activities than 1 do not react with 4 but do react very selectively with simple methylindoles to form diarylmethylated derivatives.

ChemInform Abstract: The Mechanism of Formation of 3H,9H-Pyrano(3,4-b)indol-3-ones from 3- Indolalkanoic Acids.

The mechanism of the formation of 1-methyl-3H,9H-pyrano[3,4-b]indol-3-one (4) from the corresponding 3-indolacetic acid 1 is discussed. The suggested mechanism is substantiated by the isolation of a stable intermediate 2 and its transformations in the presence of acetic anhydride and/or Lewis acids.

Reactions of electron-rich heterocycles with orthocarboxylic acid derivatives.11. Reactions of carbazole and 4-methoxycarbazole with triethyl orthoformate: Regiospecific functionalization of the carbazole nucleus

Carbazole (1a) and 4-methoxycarbazole (1b) can be regioselectively functionalized by reaction with triethyl orthoformate. Whereas the reaction of 1a with the ortho ester furnishes the amide acetal 2, the new carbazole derivatives 4–10 are formed, depending on the reaction conditions, in the electrophilic substitution of 1b. The products of this reaction sequence provide a contribution to studies on the mechanism of the transformation of 1b to tris-carbazolylmethane 5. Compound 5 represents a new, three-bladed propeller in the triheteroarylmethane series.

ChemInform Abstract: Diels-Alder Reactions of (1H-Indol-3-yl)-enacetamides and -endiacetamides: A Selective Access to Acetylamino-Functionalized (b)Anellated Indoles and Carbazoles.

ChemInform Abstract: Proton Acid-Induced Rearrangements of α-Alkynylestradiol Methyl Ethers.

When subjected to proton catalysis, the α-alkynylestradiol methyl ethers 1a and 1b furnish the Rupe or Meyer-Schuster rearrangement products 2, 4, and 5a. In the presence of sulfuric acid, α-ethynylestradiol 3-methyl ether (1a) is converted into the D-homosteroid 3a. The use of deuterated acids gives rise to the formation of the corresponding deuterated steroids 2b, 2c, 3b, and 5b. Some mechanistic implications of these results are also discussed.

Reaction of 2,2′-bis(N-methylindolyl) with dimethyl acetylenedicarboxylate and thermally- and photochemically-induced cyclizations of the product

2,2′-Bis(N-methylindolyl) 1 reacts with dimethyl acetylenedicarboxylate to furnish the 3-dimethyl maleoyl-substituted 2,2′-bisindolyl 2. Compound 2 cyclizes under aluminum trichloride catalysis according to a polar process to give a cyclopenta[2,1-b:3,4-b′]diindole derivative 4. Reaction of compound 4 with benzyl-amine yields the spiro derivative 5. Photochemically-induced 1,6-electrocyclization of compound 2 gives rise to the indolo[2,3-a]carbazole 6 directly, which is readily transformed to the pyrrolo-annelated carbazole 7 by treatment with benzylamine.

New structural aspects of 3-vinyl-1H-indoles for predicting the outcome of Diels-Alder reactions

Some selected 3-vinyl-1H-indoles have been synthesised and the first13C-NMR studies performed; in addition He(Iα) photoelectron spectra and the results of perturbation MO calculations of some examples of this class of compounds are presented. The molecular characteristics obtained thereby can be used to predict the results of [π4s+π2s]-cycloaddition reactions with 3-vinylindoles.

Zur protonenkatalysierten elektrophilen substitution von 2,3-dimethylindol mit arylaldehyden: C6-regioselektivität am indol-gerüst

The proton catalyzed reaction of 2,3-dimethylindole (1) with several arylaldehydes 2 yields the 6,6′bisindolylarylmethanes 5 regioselectively. No mechanistic information about the predominant attack of the aldehydes on the indole nucleus is obtained, because the reaction proceeds too fast to control. The electron-rich aldehydes, 2,4,6-trimethoxybenzaldehyde and indole-3-carbaldehyde, yield exclusively the 6,6′,6″-trisin-dolylmethane 9. The constitutions of all isolated methanes were elucidated by 400 MHz 1H-nmr spectroscopy.

Zur Reaktion vonE/Z-N-Benzolsulfonyl-3(2-methoxyvinyl)-indol mit Carbo- und Heterodienophilen: NeueDiels-Alder-Addukte aus der Indol- bzw. Carbazol-Reihe, V

E/Z-Benzenesulfonyl-3(2-methoxyvinyl)-indole1 reacts viaDiels-Alder type mechanism with dimethyl acetylendicarboxylate, N-phenyltriazolindione and diethyl mesoxalate to give new cycloadducts2–5 with [b]annellated indole structures.

Advances in DNA-ligands with groove binding, intercalating and/or alkylating activity: chemistry, DNA-binding and biology.

It is known that DNA is a well-characterized intracellular target but its size and sequential characteristics make it an elusive target for selective drug action. Binding of low molecular weight ligands to DNA causes a variety of significant biological responses. In this context the main consideration is given to recent developments in DNA sequence selective binding agents bearing conjugated effectors because of their potential application in treatment of cancers, in diagnosis as well as in molecular biology. In the present review recent results about analogues of netropsins, distamycin A and of some lexitropsins and combilexins or related hybrid molecules with sequence reading, intercalati…

ChemInform Abstract: Design, Synthesis, DNA-Binding and Cytotoxicity Evaluation of New Potential Combilexines.

Combilexines, compounds in which a DNA intercalator is linked to a minor groove binding component, interact with the DNA in a sequence specific manner to yield in most cases compounds with anticancer activity. A series of new compounds closely related to netropsin in which the two components were linked by an amide group was synthesised as potential combilexines. As some of these compounds showed cytotoxic activity in vitro, an attempt was made to rationalise their mechanism of action. The DNA binding characteristics of the carboxamides were evaluated by thermal denaturation experiments and by ethidium bromide displacement assay. Their ability to inhibit the topoisomerase I was also determi…

ChemInform Abstract: Advances in Indolo[2,3-a]carbazole Chemistry: Design and Synthesis of Protein Kinase C and Topoisomerase I Inhibitors

Indolo[2,3-a]carbazoles, their pyrrolo[3,4-c]anellated variants and structurally closely related bisindolylmaleimides represent a biologically highly interesting class of natural compounds which are potential anticancer agents. According to the ongoing literature new and efficient synthetic methods yield a great variety of these compounds which have been reported in detail. The biological activities and the inhibitory activities against the target enzymes protein kinase C and topoisomerase I are also discussed including structure activity relationships. A molecular binding model of the protein kinase C inhibitors with the target enzyme at the atomic level is presented and supported by X-ray…

Bis[indanyl]- and bis[indenyl]arylmethanes: New molecular three-bladed propellers

Proton-catalyzed arylmethylation of indan and indene derivatives with 4-methoxybenzaldehyde yield novel triarylmethanes bearing indan or indene substituents. According to Mislow's definition, these molecules belong to the class of molecular three-bladed propellers and exhibit an interesting stereochemistry.

Proton Acid-induced Rearrangements of α-Alkynylestradiol Methyl Ethers

When subjected to proton catalysis, the α-alkynylestradiol methyl ethers 1a and 1b furnish the Rupe or Meyer-Schuster rearrangement products 2, 4, and 5a. In the presence of sulfuric acid, α-ethynylestradiol 3-methyl ether (1a) is converted into the D-homosteroid 3a. The use of deuterated acids gives rise to the formation of the corresponding deuterated steroids 2b, 2c, 3b, and 5b. Some mechanistic implications of these results are also discussed.

Ein Fortschritt in der Arzneistoff-forschung: Rationales Wirkstoffdesign mit der Kombinatorischen Chemie

Elektronenstoß-induzierte massenspektrometrische Fragmentierung von 2,2′-Bisindolylmethoxy- und Trisindolyl-methanen

Regioselektive Zinn(II)chlorid-induzierte N-Aralkoxy-alkylierung am 2,3-Dimethylindol

2,3-Dimethylindole (1) reacts by tin(II)chloride catalysis with arylaldehydes in dichloromethane, which contains 0.2% ethanol, regioselectively to the indol-1-yl-aryl-ethoxy-methanes3 a, 3 b.

ChemInform Abstract: Bis(indanyl)- and Bis(indenyl)arylmethanes: New Molecular Three-Bladed Propellers.

Proton-catalyzed arylmethylation of indan and indene derivatives with 4-methoxybenzaldehyde yield novel triarylmethanes bearing indan or indene substituents. According to Mislow's definition, these molecules belong to the class of molecular three-bladed propellers and exhibit an interesting stereochemistry.

Zur Konstitutionsaufklärung trisubstituierter Indolderivate: NMR-spektroskopische Untersuchung von Bis(2,3-dimethyl-6-indolyl)-arylmethanen

The application of combined1H- and13C-NMR-technics is used exemplarily for the elucidation of the type of substitution at the phenyl nucleus of indoles in 6,6′-bis-indolylarylmethanes (1,2). These methods can be applied in general to analogous structure problems.

Design, synthesis and biological evaluation of new oligopyrrole carboxamides linked with tricyclic DNA-intercalators as potential DNA ligands or topoisomerase inhibitors.

In the context of the design and synthesis of minor groove binding and intercalating DNA ligands some new oligopyrrole carboxamides were synthesized. These hybrid molecules (combilexins) possess a variable and conformatively flexible spacer at the N-terminal end. As intercalating tricyclic systems acridone, acridine, anthraquinones and in a special case iminostilbene terminate the N-terminal end of the pyrrole chain. The cytotoxicity was examined by the NCI antitumor screening, furthermore, biophysical as well as biochemical studies were performed in order to get some information about the DNA binding properties and topoisomerase inhibition effect of this new series of molecules.

Model building and molecular mechanics calculations of mitoxantrone-deoxytetranucleotide complexes: Molecular foundations of DNA intercalation as cytostatic active principle

Several intercalation complexes of the antitumor-active drug mitoxantrone with base paired tetranucleotides were constructed by molecular modeling using computer graphics and molecular mechanics calculations. The mitoxantrone molecule favours DNA binding into CG intercalation site. The two side chains of the drug are orientated into the major groove and fixed by hydrogen bonds with the nucleotide bases. This molecular study can be helpful for understanding the mode of action of cytostatically active compounds and to design new structurally related compounds of the anthraquinone drug type.

Carbazole synthesisviaanin situtrapping strategy with indolyl enol ethers

Indolyl enol ethers, generated from the alkoxy(indolyl)carbenium tetra- fluoroborates (1) by treatment with sodium hydride, can be trapped with dimethyl acetylenedicarboxylate or N-phenylmaleimide to furnish the se- lectively functionalized carbazoles (3), (4), (5), (9), (10), and (13). In addition, the biaryl derivatives (6) and (11) are produced by a ring- opening reaction of the primarily formed Diels-Alder adduct. In the case of the biaryl derivative (6), an X-ray crystal structure analysis yields valuable information on constitutions and configurations in the biaryl series. The phenomenon of atropisomerism is discussed for this compound

New electrophilic reactions of 2,2′-bisindolyls with acid chlorides and carbodienophiles

Some new acylation and cyclization reactions of 2,2′-bisindolyls 1, 2 are described. The product patterns constitute acyl derivatives 3, 4, 5 and an aldehyde 7, indolo[2,3-a]carbazoles 6, 14, 17, 19, 20 and cyclopentadiindoles 22 and 24. In the reaction with aryne or diazotated anthranilic acid, a 3-benzoylindole derivative 9 and phenylindolyl azo dye 10 are formed. N-methylmaleimide reacts with 2,2′-bisindolyl 2 via Michael type addition, dehydrogenation and cyclization to several functionalized or anellated indole derivatives 11, 12, 13 and 14, respectively.

Chemistry and biology of new marine alkaloids from the indole and annelated indole series.

Chemistry and biology of marine natural products from the indole and annelated indole series have become an attractive research field for development of new pharmacological lead substances. In the past years some of the isolated natural organic compounds were synthesized by chemists and evaluated with great enthusiasm to find new lead natural compounds against different diseases. In this review the latest results for new compounds including isolation, biological evaluation, synthetic pathways and some retrosynthetic analyses are summarized.

Reactions of 3-(tetrahydropyrid-4-yl)-indoles with dienophiles: new heterocyclic functionalized indoles and pyrido[]annellated carbazoles

First reactions of 3-(1,2,3,6-tetrahydropyrid-4-yl)-indoles 1 with a variety of carbo- and heterodienophiles are described. These reactions provide a new access to heterocyclic functionalized indoles and pyrido[c]annellated carbazoles, compounds of interest as potential antidepressive and antitumor active agents.

ChemInform Abstract: First Transformations of Pyrano(3,4-b)indol-3-ones to Salvadoricine and 2,3-Diacylindoles.

The readily available methylated pyrano[3,4-b]indol-3-ones 1a and 1b were hydrolyzed to furnish the 2-acetylindol-3-alkanoic acids 2 and 4. Compound 2 was easily transformed selectively to 2-acetyl-3-methylindole (3, salvadoricine). Substrate 1b reacts with molecular oxygen from the air only in the presence of a catalyst to give 2,3-diacetylindole (5) while 1a reacts with nitrosobenzene via a proposed Diels-Alder step to yield 2-acetylindole-3-carbaldehyde (6). The latter product can also be obtained in low yield from the reaction of 1a with molecular oxygen from the air.

First Electrophilic Substitutions of 3-Substituted Indoles with Diethoxycarbenium Tetrafluoroborate: Functionalized Indole Derivatives

The indoles 2a-2c react with diethoxycarbenium tetrafluoroborate (1) to furnish the indolecarbaldehydes 3a-3d. In the thermodynamically controlled reaction of 3-methylindole (2a) with 1 the tris(indolyl)methane 4 and diskatole (5), are formed in addition. The limitations of these reactions are discussed and evidence is presented for a C-3-ipso-attack and a Wagner-Meerwein rearrangement, respectively, leading to the formation of 3b or 3d. Erste elektrophile Substitution von 3-substituierten Indolen mit Diethoxycarbenium-Tetrafluoroborat: Funktionalisierte Indol-Derivate Die Indole 2a-2c reagieren mit dem per se synthetisierten Diethoxycarbenium-Tetrafluoroborat (1) zu den Indolcarbaldehyden …

Design, synthesis, DNA-binding and cytotoxicity evaluation of new potential combilexines

Combilexines, compounds in which a DNA intercalator is linked to a minor groove binding component, interact with the DNA in a sequence specific manner to yield in most cases compounds with anticancer activity. A series of new compounds closely related to netropsin in which the two components were linked by an amide group was synthesised as potential combilexines. As some of these compounds showed cytotoxic activity in vitro, an attempt was made to rationalise their mechanism of action. The DNA binding characteristics of the carboxamides were evaluated by thermal denaturation experiments and by ethidium bromide displacement assay. Their ability to inhibit the topoisomerase I was also determi…

ChemInform Abstract: 1,6-π-Electrocyclization of 3-Vinyl-Functionalized N,N′-Dimethyl-2,2′-bisindolyl: Some Analysis of the Educt Transformation Process.

The thermally and photochemically induced 1,6-π-electrocyclization reaction of 3-vinyl-functionalized N, N'-dimethyl-2,2′-bisindolyls 4 has been analysed and some reactivity aspects are presented. On the basis of time dependent 1H nmr and uv spectroscopic measurements the educt transformations can be observed in detail. Some results of the isomerization process of the educts are also given.

Nitrogen-Containing Hetarene Quinones

Design Synthesis and Biological/Biophysical Evaluation of New Oligopyrrole Carboxamides, Biscarbazoles, Oxocarbazoles and Benzo[a]carbazoles: Antitumor and Antioxidative Compounds

New propylamine oligopyrrole carboxamides linked to a heterocyclic or anthraquinone system: synthesis, DNA binding, topoisomerase I inhibition and cytotoxicity

Continuing our studies on combilexines, compounds consisting of a DNA intercalator linked to a minor groove ligand, new results are presented. The synthesis of a series of new propylamine oligopyrrole carboxamides closely related to netropsin and distamycin A, linked to a heterocyclic or anthraquinone system is reported. The cytotoxic activity in vitro, the DNA binding characteristics and the inhibition of the topoisomerase I of the compounds were studied in order to explain the biological mechanism of action of these new potential combilexines. Some of the synthesised compounds showed cytotoxic activity against human tumour cell lines, as well as DNA binding and topoisomerase I inhibiting …

ChemInform Abstract: Reactions of 3-Vinylindole Derivatives with Dienophiles.

Reactions of 3-(1-cyclohexenyl)-1,2-dimethylindole (1a) and the 1,2-dihydrocarbazole 1b with some carbo- and heterodienophiles are described. Thus, compound 1a reacts to give ene, Michael-type, and Diels-Alder adducts, depending on the dienophile and reaction conditions. The 3-vinylindole 1b reacts with 4-phenyl-1,2,4-triazoline-3,5-dione or N-phenylmaleimide in a dehydrogenative reaction to yield the fully aromatized carbazole 8.

Diels-Alder Reactions of (1H-Indol-3-yl)-enacetamides and -endiacetamides: A Selective Access to Acetylamino-Functionalized [b]Annelated Indoles and Carbazoles

Diels-Alder reactions of the (1H-indol-3-yl)-enacetamides and -endiacetamides 1a–d with some carbodieno-philes and 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione give rise to the novel amino-functionalized carbazole; 4–6 and 8 (Scheme 3). Ethenetetracarbonitrile reacts with 1b to furnish the Michael-type adduct 7 (Scheme 3). Structural aspects of the starting materials 1, which exhibit above all 3-vinyl-1H-indole reactivity, are discussed with regard to the prediction of a Diels-Alder process.

First reactions of dialkoxycarbenium tetrafluoroborates with pyrroles, 5H-dibenz[b,f]azepines, and electron-rich arenes

Pyrrole (2a) and 2,5-dimethylpyrrole (2b) react with the dialkoxycarbenium tetrafluoroborates 1a-1c under kinetic control to yield the corresponding acylpyrrole derivatives. 5H-Dibenz[b,f]azepine (9a) and the 10,11-dihydro derivative 9b react only with the most electrophilic of the series of electrophiles tested, namely, diethoxycarbenium tetrafluoroborate (1a), to furnish the corresponding formyl derivatives. Similarly, in arene chemistry, the highly electron-rich N,N-dimethylaniline (13a) and 1,3,5-trimethoxybenzene (13b) are formylated by reaction with 1a.

N,N-Dimethylformamide Diethyl Acetal

(1; R1 = Et, R2 = Me) [1188-33-6] C7H17NO2 (MW 147.25) InChI = 1S/C7H17NO2/c1-5-9-7(8(3)4)10-6-2/h7H,5-6H2,1-4H3 InChIKey = BWKAYBPLDRWMCJ-UHFFFAOYSA-N (2; R1 = Me, R2 = Me) [4637-24-5] C5H13NO2 (MW 119.19) InChI = 1S/C5H13NO2/c1-6(2)5(7-3)8-4/h5H,1-4H3 InChIKey = ZSXGLVDWWRXATF-UHFFFAOYSA-N (3; R1 = PhCH2, R2 = Me) [2016-04-8] C17H21NO2 (MW 271.39) InChI = 1S/C17H21NO2/c1-18(2)17(19-13-15-9-5-3-6-10-15)20-14-16-11-7-4-8-12-16/h3-12,17H,13-14H2,1-2H3 InChIKey = JFIKHFNGAURIIB-UHFFFAOYSA-N (4; R1 = Et, R2 = Et) [22630-13-3] C9H21NO2 (MW 175.31) InChI = 1S/C9H21NO2/c1-5-10(6-2)9(11-7-3)12-8-4/h9H,5-8H2,1-4H3 InChIKey = AYZXEGOJMRKZCV-UHFFFAOYSA-N (mild and selective reagents for alkylation, f…

New Studies and a Reinvestigation on [4+2] Cycloadditions of (−)-Thebaine: Asymmetrical Diels-Alder Reactions with a Conformationally Fixed Chiral Diene

Some novel Diels-Alder reactions of the opium alkaloid (−)-thebaine (1) as an electron-rich diene and a reinvestigation of its reactions with cyclic and acyclic dienophiles are described. The π-facial selectivity has been studied on the basis of structural analyses of the cycloadducts. Some related results on [4 + 2] cycloaddition reactions of 1-methoxy-1,3-cyclohexadiene (11) are also reported.

Reactions of Pyrano[3,4-b]indol-3-ones with Dienophiles: Consecutive [4 + 2] Cycloaddition/Cycloreversion/1,2 Elimination

Methylpyrano[3,4-b]indol-3-ones 1 react with selected dienophiles (as acetylene equivalents) in a consecutive Diels-Alder/cycloreversion/1,2 elimination reaction sequence to furnish the 1-methyl- and 1,4-dimethylcarbazoles 4.

Zur protonenkatalysierten Aralkylierung von 1,2,3-Trimethylindol und 1,2,3,4-Tetrahydrocarbazol mit Arylaldehyden

1,2,3-Trimethylindol (2) liefert mit Benzaldehyden die Kondensationsprodukte 5 und 6, wahrend aus den NH-Indolen 1 und 3 die Verbindungen 7 und 8 entstehen. Proton-catalyzed Aralkylation of 1,2,3-Trimethylindole and 1,2,3,4-Tetrahydrocarbazole with Arylaldehydes Reaction of 1,2,3-trimethylindole (2) with benzaldehydes leads to the condensation compounds 5 and 6, the NH-indoles 1 and 3, however, give 7 and 8.

Zur Struktur der Produkte der Reaktion vonE/Z-1-Benzolsulfonyl-3-(1-pentenyl)-indol mit N-Phenylmaleinimid: Ein erster Beitrag zur Konfigurations- und Konformationsanalyse in der Vinylindol-Cycloadditionsreihe

The products2,3 of the reaction ofE/Z-1-benzenesulfonyl-3-(1-pentenyl)-indole (1) and N-phenylmaleimide were analysed by1H-NMR spectroscopy. Exemplarily, the structure elucidation of theendo-cyclo-adduct2 b was achieved by using several NMR techniques (diff. NOE-, INDOR-measurements, decoupling experiments, spectra simulation). The1H-NMR-spectroscopically gained prediction of relative configuration and conformation of2 b was supported on X-ray analysis. The cyclohexene ring of the new cycloadducts adopts in the liquid phase and in the crystal a slightly twisted boat conformation.

Reactions of 1-isopropyl-3-methyl- and 2,3-dimethylindoles with triethyl orthoformate: New trisindolylmethanes

Indoles 1 and 2 react with triethyl orthoformate under proton–catalyzed conditions to form trisindolylmethanes. The regioisomer distribution of the products is controlled by steric and electronic factors.

Advances in Marine Natural Products of the Indole and Annelated Indole Series: Chemical and Biological Aspects

Marine natural products, form a field of scientific endeavour, that has recently grown considerably. The isolation, biological evaluation, chemical properties and synthetic elaborations of products of marine organisms have attracted the attention of organic chemists, medicinal chemists, biologists and pharmacists. In this context a structurally and biologically highly interesting class is represented by the marine natural products containing an indole moiety in a pure substituted form or in an anellated form. The present review summarizes primarily the actual results concerning these products as new pharmacologically attractive lead compounds for drug design. The chemistry, biological evalu…

ChemInform Abstract: Reaction of 2,2′-Bis(N-methylindolyl) with Dimethyl Acetylenedicarboxylate and Thermally and Photochemically Induced Cyclizations of the Product.

2,2′-Bis(N-methylindolyl) 1 reacts with dimethyl acetylenedicarboxylate to furnish the 3-dimethyl maleoyl-substituted 2,2′-bisindolyl 2. Compound 2 cyclizes under aluminum trichloride catalysis according to a polar process to give a cyclopenta[2,1-b:3,4-b′]diindole derivative 4. Reaction of compound 4 with benzyl-amine yields the spiro derivative 5. Photochemically-induced 1,6-electrocyclization of compound 2 gives rise to the indolo[2,3-a]carbazole 6 directly, which is readily transformed to the pyrrolo-annelated carbazole 7 by treatment with benzylamine.

ChemInform Abstract: First Synthesis of Chiral 3-Vinylindoles as 4π-Components for Diels- Alder Reactions.

The first syntheses of chiral 3- and 2-vinylindoles bearing sulfoxide or (-)-menthyloxy functional groups at the β-vinyl positions by way of procedures based on the Horner-Wadsworth-Emmons and Wittig reactions, respectively, are described. Some Diels-Alder reactions demonstrating the 4π-reactivity of these compounds are reported.

ChemInform Abstract: New Reactions of Vinylindoles as Heterocyclic Dienes with 4-Phenyl-1,2,4-triazoline-3,5-dione: Non-Concerted versus Concerted Processes.

ChemInform Abstract: Electrophilic Substitution and Cyclization of 2,2′-Bis(N-methylindolyl) : A Simple Access to Potential Protein Kinase C Inhibitor.

A strategy is described for the synthesis of functionalized and cyclized 2,2′-bisindolyl derivatives related to several basic systems of natural products. The starting 2,2′-bis(N-methylindolyl) (8) reacts with a variety of electrophiles and electrophilic dienophiles to furnish the novel, functionalized and cyclized bisindolyl derivatives 9–16. In addition, some reactivity and structural aspects are discussed; an X-ray crystallographic analysis of the 2,2′-bisindolyl 8 provided valuable information for the conformational analyses.

Zur Regiochemie von [4 + 2]-Cycloadditionen mit Methylpyrano[3,4-b]indol-3-onen und unsymmetrischen Dienophilen

Die methylierten Pyrano[3,4-b]indol-3-one 1a, 1b reagieren mit acyclischen, unsymmetrischen CC-Dienophilen nach einer Diels-Alder-Reaktion/CO2-Extrusion zu selektiv funktionalisierten Carbazolen 2. In Abhangigkeit von der Struktur der Reaktionspartner wird keine oder geringe bis hohe Regioselektivitat festgestellt. Diethylmesoxalat reagiert mit 1a, 1b regioselektiv zu neuen 2,3-difunktionalisierten Indolen 4a, 4b, die aus einer regiokontrollierten [4 + 2]-Cycloaddition und Cycloreversion resultieren, wobei Pyrano[3,4-b]indoldicarbonsaure-diethylester 3a, 3b als Intermediate auftreten durften. Regiochemistry of [4 + 2] Cycloadditions with Methylpyrano[3,4–b]indol-3-ones and Unsymmetric Dieno…

ChemInform Abstract: Synthetically Attractive Indolization Processes and Newer Methods for the Preparation of Selectively Substituted Indoles

The synthetically interesting processes available for indolization reactions are discussed and illustrated in tabular form and particular emphasis is placed on the more recent methods.

ChemInform Abstract: Thermal 1,6-Electrocyclization Reactions of Acceptor-Substituted 2,3-Divinyl-1H-indoles Yielding Functionalized Carbazoles.

Three new synthetic procedures for and thermal 1,6-electrocyclizations of acceptor-substituted 2,3-divinyl-1H-indoles leading to functionalizing carbazoles are described. The scope and limitations as well as some mechanistic aspects of the methodologies are discussed. The key strategies employed include Pd(II)-catalyzed coupling and Wittig procedures.

ChemInform Abstract: New Structural Aspects of 3-Vinyl-1H-indoles for Predicting the Outcome of Diels-Alder Reactions

Some selected 3-vinyl-1H-indoles have been synthesised and the first13C-NMR studies performed; in addition He(Iα) photoelectron spectra and the results of perturbation MO calculations of some examples of this class of compounds are presented. The molecular characteristics obtained thereby can be used to predict the results of [π4s+π2s]-cycloaddition reactions with 3-vinylindoles.

ChemInform Abstract: New Reactions of 2- and 3-Vinylindoles with Azodienophiles, Diethyl Mesoxalat, and Nitrosobenzene: An Access to Functionalized and (b)Anellated Indoles.

Synthetically attractive indolization processes and newer methods for the preparation of selectively substituted indoles

The synthetically interesting processes available for indolization reactions are discussed and illustrated in tabular form and particular emphasis is placed on the more recent methods.