Three-Component,Four-Molecule,Ru-Catalyzed Cascade Reactions of Indoles and Alkyl Bromides with Sodium Nitrite

Abstract

An operationally simple domino approach for the ruthenium-catalyzed synthesis of (E)-2,3′-bi(3H-indol)-3-one O-alkyl oximes by the region- and stereoselective three-component, four-molecule reactions of indoles with sodium nitrite and alkyl bromides under mild reaction condition in dimethylformamide is described. Remarkably, multiple bonds including C?C, C=N, and C?O bonds were conveniently formed in one pot. The reaction is tolerant to air and is atom economical, in accordance with the concept of modern green chemistry.     

Facile and efficient synthesis of a new class of bis(3′-indolyl)pyridine derivatives via one-pot multicomponent reactions

A series of 4-aryl-3,5-dicyano-2,6-di(3′-indolyl)pyridine derivatives were synthesized via a one-pot multicomponent reaction of aromatic aldehydes, 3-cyanoacetyl indoles, and ammonium acetate under microwave irradiation. Particularly valuable features of this method include high yields of products, broad substrate scope, short reaction time, and straightforward procedure.     

A tandem highly stereoselective FeCl3-promoted synthesis of a bisindoline: synthetic utility of radical cations in heterocyclic construction

A conceptually distinctive stereoselective construction of the novel dimer, N-[N′-acetyl-7,7′-bis-(3,4-dimethoxy-phenyl)-7,8,7′,8′-tetrahydro-N′H-[8,8′]biindolyl-N-yl]-ethanone 25 (bisindoline) is described below. These structures, which include 7-(3,4-dimethoxyphenyl)-indoline 24 (veratryl indoline), were obtained by the tactical combination of palladium-catalysed coupling which produced 10-acetamido-3,4-dimethoxystilbene 9, followed by FeCl₃ induced oxidative cyclization/dimerization. All new structures were fully characterized by 1- and 2D NMR spectroscopy, (proton, carbon-13, COSY, HMBC, HMQC) and mass spectrometry. Configurational assignments were further supported by semi-empirical AM1 calculations. Mechanistic interpretations, consistent with our results, are discussed.     

Synthesis and MRSA PK inhibitory activity of thiazole containing deoxytopsentin analogues

The public health care crisis caused by the emergence of drug resistant bacterial strains, e.g., methicillin resistant Staphylococcus aureus (MRSA) has underlined the urgent need to accelerate the discovery of new chemical entities active against antibiotic resistant bacteria. We report here the synthesis of a series thiazole containing deoxytopsentin analogues, which show moderate activity against a target MRSA pyruvate kinase enzyme: an evolutionary conserved hub protein critical for bacterial survival. A Hantzsch thiazole coupling between α-oxo-1H-indole-3-thioacetamides and 2-bromo-1-(1H-indol-3-yl)-ethanones provided facile access to the thiazole containing deoxytopsentin compounds.     

TEMPO-catalyzed oxidative dimerization and cyanation of indoles for the synthesis of 2-(1H-indol-3-yl)-3-oxoindoline-2-carbonitriles

A method for the combinative oxidative homo dimerization and cyanation of free indole derivatives catalysed by TEMPO along with silver carbonate was demonstrated for the first time This new methodology is both atom and step efficient and is applicable to a broad scope of substrates, allowing the synthesis of a range of synthetically valuable 2-(1H-indol-3-yl)-3-oxoindoline- 2-carbonitriles in moderate to excellent yields. Furthermore, selected compounds 6b and 6g exhibit moderate to good anti-schistosomicidal activities.     

Synthetic studies towards dendridine A: synthesis of hemi-dendridine A acetate by Fischer indolization

A short synthesis of hemi-dendridine A acetate has been accomplished. The synthesis is based on a modified Fischer indolization that represents a rare example of the single-step synthesis of a 7-oxytryptamine from an ortho-oxygenated phenylhydrazine. The synthetic route required developing an efficient synthesis of N-acetyl-2-pyrroline, the key coupling partner for the modified Fischer indolization. Some interesting chemistry associated with the abnormal Fischer indolization has been uncovered, whereby two molecules of the phenylhydrazine substrate combined along the abnormal reaction pathway, affording an unusual N-phenylindoleamine product.     

An Easy and Efficient Synthesis of Bisindolylmethanes and Tetraindolylmethane Tröger's Base Catatlyzed by AgBF4

This work presents a highly efficient and simple method for the synthesis of bisindolylmethanes, catalyzed by AgBF₄, with excellent yields. Various substituted aldehydes and ketones with indole under this reaction condition is elucidated. This reaction occurs efficiently under mild reaction conditions, such as are applied with methoxy or furfural, which commonly undergoes cleavage under strongly acidic reaction conditions. The presented approach was suitable for the synthesis of complex systems, such as tetraindolylmethane Tröger's Base.     

Antiviral enantiomers of a bisindole alkaloid with a new carbon skeleton from the roots of Isatis indigotica

A pair of indole alkaloid enantiomers with a novel bisindolylacetamide skeleton, insatindibisindolamides A and B (1a and 1b), was isolated from an aqueous extract of Isatis indigotica roots. The enantiomers were separated by chiral HPLC. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, including 2D NMR, X-ray crystallography, and electronic CD (ECD) calculation. The proposed biosynthetic pathway and preliminary investigations of the biological activity of compounds 1a and 1b are also discussed.     

On the biosynthesis and optical activity of the flinderoles

A proposed biosynthesis of the flinderoles described herein would produce racemic compounds through nonenzymatic dimerization of borrerine. However, an initial report of optical activity for natural flinderoles is inconsistent with that hypothesis as well as the racemic production of similar natural products. Herein, pure enantiomers of flinderole B were obtained and the specific rotations thereof were found to be significantly different from those in the original report, which were taken at low concentrations. These new data remove the inconsistency arising from the original data.     

Xenocladoniamide F,minimal indolotryptoline from the cladoniamide pathway

The isolation and structure elucidation of indolotryptoline alkaloid xenocladoniamide F (8) from a cladoniamide heterologous production system is reported. The structure of 8 is determined by NMR and X-ray crystallography. Relative to the parent cladoniamides, 8 lacks any remnant of an N-methylsuccinimide ring. This pentacyclic alkaloid is the most minimal indolotryptoline natural product yet reported.