Synthesis and preliminary cytotoxic evaluation of substituted indoles as potential anticancer agents

A variety of indole derivatives were designed,synthesized and preliminarily evaluated for their in vitro cytotoxic activity in the A431 and H460 cell lines.All the compounds examined conferred unusual potency in a tumor cell cytotoxicity assay.The findings showed the indole derivatives would be a promising candidate for the development of new anticancer agents.     

A Convenient and Efficient Route to 1,4-Bis（heteroaryl）-buta-1,3-diene and 4-Heteroarylbut-1-en-3-yne from 1,4-Dichlorobut-2-yne

A convenient and practical route to functionalized conjugated 1,3-enynes and 1,3-dienes is described. 1,4-Bis（heteroaryl）- 1,3-diene and 1-heteroarylbut- 1-en-3-yne derivatives were prepared from 1,4-dichloro-2-butyne and corresponding N-heteroarenes such as imidazole, pyrrole, pyrazole and indole derivatives in the presence of bases in good to high yields.     

A Facile Synthesis of Indole-based Conjugated Derivatives

A novel synthetic method was developed for the preparation of indole-based conjugated derivatives with satisfied yields. By applying this strategy, a series of new compounds were prepared conveniently. All the obtained new indole derivatives were characterized by spectroscopic analyses, giving satisfactory data corresponding to their expected molecular structures.     

Synthesis of a Pair of Derivatives of N-Methylpyrrole Polyamide

A pair of derivatives of tetrameric N-methylpyrrole polyamide were synthesized in order to develop a new method for the study of interaction of the polyamide derivatives with DNA. Indole acetic acid and nicotinic acid were introduced to the polyamide in the synthesized compound, which showed an expected red shift in the UV spectrum. These compounds may function as a potential tool in the detection of the polyamide binding to DNA.     

Studies on the biological activity of gem-difluorinated 3,3-spirocyclic indole derivatives

The biological activities of a series of 3,3-spirocyclic indole derivatives containing CF₂, phosphine oxide,indole, and cyano functional groups were evaluated, and these derivatives were found to exhibit antiTMV, fungicidal, and insecticidal activities.     

Catalytic Reaction of Aryldiazoacetates with Indole and Its Derivatives:Profound Effect of N‐1 Substitutent on the Reaction Pathways

The reaction of indole and its derivatives with aryldiazoacetates has been studied in the presence of copper and rhodium catalysts. The electronic property of N-1 substitutent showed significant effect on the reaction pathways. The electron-donating group favored the formation of the β-alkylation products, while the electron-withdrawing group favored the formation of the cyclopropane products. A reaction mechanism was proposed based on the experimental data and previous research results. The structure of aryl group in diazo compounds also affected the yield of the β-alkylation products or the cyclopropane products.     

An efficient way to coupling amine with derivatives of steric N-Boc-pyrrolidine-2-carboxylic acid

An efficient way to coupling amine with the derivatives of steric N-Boc-pyrrolidine-2-carboxylic acid was reported in this paper.We have found that the synthesis of derivatives is problematic with the commonly used DCC/HOBT method.As a substitute,themixed anhydride method was adopted.A series of 6-(3-nitroguanidino)hexanamidopyrrolidine derivatives were prepared with thismethod.     

BF_3-promoted annulation of azonaphthalenes and ynamides for synthesis of benzo[e]indoles

A novel BF₃-promoted [3+2] annulation of azonaphthalenes and ynamides is described.This protocol provides a modular and efficient entry to functionalized amino benzo[e]indole derivatives smoothly.     

K3PO4-Catalyzed Regiospecific Bromoamidation of β, β-Dicyanostyrene Derivatives with N-Bromoacetamide（NBA）

An efficient method for the bromoamidation of β,β-dicyanostyrene derivatives with N-bromoacetamide （NBA） was developed.This protocol provides a convenient process to convert β,β-dicyanostyrene derivatives into the vicinal haloamines in excellent yields（up to 99％） at room temperature in the presence of anhydrous K3PO4 as a catalyst without the protection of the inert gaseous in CH2Cl2.A total of 11 examples were investigated and all the products showed the regionspecific feature.Based on the observation of different activities for the different substrates involving the electron-rich or electron-deficient β,β-dicyanostyrenes,a possible Michael addition mechanism was proposed.     

Triazole-gold (TAAu) catalyzed three-component coupling (A3 reaction) towards the synthesis of 2, 4-disubstituted quinoline derivatives

A gold-catalyzed three-component coupling reaction (A3 reaction) was developed as an efficient approach for the synthesis of challenging 2,4-disubstituted quinoline derivatives. Compared to previously reported Cu/Au bi-catalyst system, this protocol enables achieving A3 reaction only in the presence of triazole-gold catalyst. Notably, 4-alkyl substituted or 2-alkyl substituted quinoline derivatives were obtained with good yields, which highlighted the unique advantage of this new strategy.     

On the Synthesis and Reactions of Indole-2-carboxylic Acid Hydrazide

Summary.  Indole-2-carboxylic acid hydrazide was prepared and allowed to react with aromatic aldehydes in acidic medium to give the corresponding hydrazone derivatives in good yields. The hydrazones were cyclized to indolo[2,3-d]pyridazine derivatives by refluxing with acetyl chloride. The indole carbohydrazide was converted to 2-triazolylindoles which acted as starting materials for several indole derivatives. A number of new indole derivatives were also prepared and structurally confirmed. Received October 17, 2000. Accepted (revised) December 12, 2000     

Characterizing the electrospray ionization mass spectral fragmentation pattern of indole derivatives synthesized from 2-keto glycosides

Four indole derivatives synthesized from 2-keto glycosides were analyzed by electrospray ionization tandem mass spectrometry (ESI-MSn) with low-energy collision-induced dissociation to establish a general structural elucidation of indole derivatives. Their fragmentation pathways are proposed on the basis of the MSn studies and deuterium-labeled experiments. Indole derivatives undergo complicated gas-phase rearrangements in addition to simple bond cleavages. A rearrangement, which involves a contraction of the six-membered ring, was observed and a mechanism was proposed. The observations may have some potential applications in the interpretation of the mass spectra of indole derivatives.     

Unexpected formation of fluorine-containing tetrahydrocarbazole during the reaction of indole, paraformaldehyde, and fluorine-containing β-ketoesters

A surprise and mild method to prepare fluorine-containing indole derivatives through a one-pot three-component condensation reaction sequence is presented. To our surprise, during the reaction of preparation of fluorine-containing indole derivatives, unexpected formation of fluorine-containing tetrahydrocarbazole was found. Moreover, this method has been demonstrated in the preparation of functionalized polycyclic indole derivatives in a straightforward and atom-economical manner.     

One-pot,three-component synthesis of highly functionalized pyrimidone derivatives and access to indole fused pyrimidones via palladium-catalyzed intramolecular Heck reaction

A simple and facile approach to highly functionalized pyrimidone derivatives and indole fused pyrimidones has been developed. The synthesis of substituted pyrimidone derivatives in moderate to good yields involves [4+2] cycloaddition of 1,4-dipoles generated from α,β-unsarurated imines and dimethyl acetylenedicarboxylate (DMAD) with isocyanates as dipolarophiles. Furthermore, the pyrimidones resulted from 2-bromophenyl isocyanate could be transformed into various indole fused pyrimidones via intramolecular palladium-catalyzed Heck reaction under different conditions.     

Synthesis and properties of [1,4]diazepino[6,5-b]indoles

1-Aryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole N-oxides were synthesized based on 3-(N"-aryl-N"-chloroacetyl)amino-2-formylindoles. Deoxidation of 2-oxo-1-phenyl-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole N-oxide afforded 1,2,3,6-tetrahydro- and 1,2,3,4,5,6-hexahydro[1,4]diazepino[6,5-b]indole derivatives. A new approach to the synthesis of pyrido[3,2-b]indole and pyrimido[5,4-b]indole derivatives was developed.     

Pd-catalyzed intramolecular oxidative C-H amination: synthesis of carbazoles

A Pd-catalyzed oxidative C-H amination of N-Ts-2-arylanilines under ambient temperature using Oxone as an inexpensive, safe, and easy-to-handle oxidant has been developed. This process represents a green and practical method for the facile construction of carbazoles with a broad substrate scope and wide functional group tolerance.     

Novel synthesis of indolylquinoline derivatives via the C-alkylation of Baylis-Hillman adducts

A new and simple method for the C-alkylation of indoles by various Baylis-Hillman adducts and the one-pot reductive cyclization of C-alkylated indole derivatives generated from 2-nitro-Baylis-Hillman adduct to form indolylquinoline derivatives is described.     

Synthesis of macrocyclic systems derived from di-(2-indolyl)heteroarenes

A number of new 3,6-di-(2-indolyl)-dibenzofuran and carbazole derivatives have been prepared from dibenzofuran and carbazole linkers via the Fischer indole synthesis. The bis-indoles were successfully formylated at C3 and the resulting dicarbaldehydes were combined with diamines to generate indole based imine macrocyclic systems.     

Enantioselective C2-Alkylation of Indoles through a Redox-Relay Heck Reaction of 2-Indole Triflates

A palladium-catalyzed enantioselective redox-relay Heck reaction of 2-indole triflates and disubstituted alkenes is reported. This process combines readily available indole triflates with a variety of alkenes to afford a range of indole derivatives bearing a stereocenter adjacent to C2. Enantioselectivity is achieved through use of a simple pyridine-oxazoline ligand. Tuning the electronics of the indole, through judicious choice of N-protecting group, is required to ensure selective β-hydride elimination away from the indole core. Utility of this method is highlighted in a modular formal synthesis of an S1P₁ agonist precursor developed by Merck.     

Et2Zn-catalyzed intramolecular hydroamination of alkynyl sulfonamides and the related tandem cyclization/addition reaction

Intramolecular hydroamination of alkynyl amides was effected by a catalytic amount of Et2Zn (20 mol %) to form indole derivatives, and a tandem cyclization/nucleophilic addition procedure involving reaction of the indole zinc salt intermediate with acid chlorides or halides was developed to provide an efficient approach to C3-substituted indole derivatives when an excess of Et2Zn (120 mol %) was used.