An efficient synthesis of highly substituted pyrrole and bis pyrrole derivatives

An efficient synthesis of highly substituted pyrrole and bis pyrrole derivatives is reported.     

Solvent‐free synthesis of pyrrole derivatives

A one‐pot synthesis of pyrrole derivatives via reaction between activated carbonyl compounds, primary amines, and 1,3‐dicarbonyls under solvent‐free conditions is described. J. Heterocyclic Chem., (2012).     

A novel tandem ene/Prins cyclization for the synthesis of octahydropyrano[2,3-c]pyrrole derivatives

A tandem ene/Prins cyclization of olefin tethered aldehyde with an aldehyde has been accomplished using 5 mol % scandium triflate at ambient temperature to afford a novel series of cis-fused octahydropyrano[2,3-c]pyrrole derivatives in good yields with high selectivity. This is the first report on a tandem cyclization of 4-methyl-N-(3-methylbut-2-enyl)-N-(2-oxoethyl)benzenesulfonamide with aldehydes.     

Remarkable solvent effect in Barton-Zard pyrrole synthesis: application in an efficient one-step synthesis of pyrrole derivatives

A unique solvent effect encountered in the Barton-Zard pyrrole synthesis was exploited to develop an efficient synthesis of pyrrole-2-esters. The chemistry was extended to a one-pot synthesis of pyrrole-2,4-dicarboxylates.     

Facile synthesis of some novel pyrrole and pyridazinoquinazolone derivatives

3-Dicyanomethylene-3-phenylpropionitrile coupled with diazotized aromatic amines (Ar-NH₂) to afford hydrazono derivatives. The latter (Ar = C₆H₅, 4-CH₃C₆H₄, 4-CH₃OC₆H₄, and 4-ClC₆H₄) were readily cyclized upon reflux in aqueous NaOH to 3(2H) pyridazinimine derivatives, which were readily transformed into their corresponding pyridazinone derivatives on reflux in ethanolic HCl. The pyridazinimines undergo reductive cleavage and recyclization via loss of ammonia to afford the corresponding N-aryl pyrroles on reflux in glacial acetic acid with Zn dust. The pyridazinone derivatives, however, undergo the same reaction but with loss of the aromatic amine moiety to afford only one pyrrolone derivative. The hydrazono derivative (Ar = 2-NCC₆H₄) was cyclized into pyridazino[3,2-b]quinazolin-6-imine, which is easily converted into pyridazino[3,2-b]quinazolin-6-one on reflux in ethanolic HCl. The latter compound is also obtained from the hydrazo derivatives (Ar = 2-HOOCC₆H₄ and 2-MeOOCC₆H₄) by reflux in aqueous NaOH.     

New polymeric derivatives of betulin

Betulin monomaleate was synthesized by reaction of betulin with maleic acid in the presence of dicyclohexylcarbodiimide, and its copolymers were prepared.     

One-pot synthesis of 5-amino 4-cyano pyrrole derivatives

One-pot synthesis of 5-amino 4-cyano pyrrole derivatives is herein disclosed. The described method consists of four steps and gives new pyrrole derivatives in moderate to good yields. This synthesis can be used for a large scale preparation.     

2,3-Dihydro-1H-1,3-diazepin-2-ones: synthesis and novel rearrangements into pyrrole derivatives

A novel synthesis of 2,3-dihydro-1H-1,3-diazepin-2-ones based on thermal elimination of methanol from 4-methoxy-2,3,4,5-tetrahydro-1H-1,3-diazepin-2-ones has been developed. The prepared dihydrodiazepinones underwent two new rearrangements under basic or acidic conditions to give the pyrrole derivatives, 3-(aminomethylene)-2,3-dihydro-1H-pyrrol-2-ones and 1-carbamoyl-1H-pyrroles, respectively. Plausible mechanisms for the rearrangements are proposed.     

Three-component domino reaction synthesis of highly functionalized bicyclic pyrrole derivatives

An efficient one-pot synthesis of highly functionalized bicyclic pyrrole derivatives by a three-component domino reaction of heterocyclic ketene aminals (HKAs), arylglyoxal monohydrate, and indoles in ethanol medium catalyzed by acetic acid is described. In this procedure, three sigma bonds were formed simultaneously. The present synthesis features excellent regio-selectivity, easy purification as well as simple starting materials.     

A novel one-pot synthesis of some new interesting pyrrole derivatives

[reaction: see text] 11-(1H-Pyrrol-1-yl)-11H-indeno[1,2-b]quinoxaline and 3-(1H-pyrrol-1-yl)indolin-2-one derivatives have been synthesized in good yields in a novel, one-pot, and efficient process by condensation of 11H-indeno[1,2-b]quinoxalin-11-one or isatin derivatives with 4-hydroxyproline on solid-support montmorillonite K10 under microwave irradiation.     

Copper catalyzed synthesis of highly substituted pyrrole and isoindole derivatives

We have developed an efficient synthesis of highly substituted pyrrole and isoindole derivatives using copper(I) catalyst. This methodology is helpful for the synthesis of some quinones bearing annealed N-heterocyclic natural products.     

Synthesis and cytotoxic activities of pyrrole[2,3-d]pyridazin-4-one derivatives

1-Methyl-2-phenyl (1) and 1,3-dimethyl-2-phenyl (2)-substituted pyrrole[2,3-d]pyridazinones, as well as their tetracyclic analogues 3-6, were synthesized and evaluated in vitro by the National Cancer Institute against 60 human tumor cell lines derived from nine cancer cell types. Biological results showed that the antitumor activities of these compounds were related to the planarity of their ring systems with potency increasing in the order 2<4 congruent with 5<6<3. Among them, the most potent compound 3 showed significant cell line cytotoxicity, particularly against the renal cancer subpanel [GI(50) (microM) 5.07] and displayed significant potency [GI(50) (microM) 3.04-4.32] against MOLT-4, SR (leukemia), NCI-H460 (non-small cell lung), HCT-116 (colon), and SF-295 (CNS) cancer cells, respectively.     

Synthesis of pyrrole urea and pyrrole carbonylurea derivatives

A series of urea and carbonylurea distamycin analogs whereby the linker has two NH groups for hydrogen bonding with base pairs of DNA were synthesized. The urea and carbonylurea derivatives are prepared from the in situ generation of pyrrole isocyanate (prepared from compound 3) and acyl isocyanate (compound 9), followed by the reaction with an amine. The synthetic feasibility for the further transformations of the pyrrole urea and pyrrole carbonylurea derivatives was also addressed. The binding abilities of these molecules to calf thymus DNA were evaluated by DNA melting temperature (T_m) analysis.     

Asymmetric synthesis of trans-2,3-disubstituted indoline derivatives

A novel method for asymmetric synthesis of trans-2,3-disubstituted indolines has been developed. The strategy involves the (-)-sparteine-mediated electrophilic substitution of 2-benzyl N-pivaloylaniline with aromatic or α,β-unsaturated aldehydes and subsequent intramolecular nucleophilic substitution. The simple protocol for two-step process can produce highly enantioenriched indolines 3a-o up to 98:2 er.     

An entry into hexahydro-2H-thieno[2,3-c]pyrrole 1,1-dioxide derivatives

Hexahydro-2H-thieno[2,3-c]pyrrole is proposed as a low molecular weight polar scaffold to construct compound libraries used in the search for new drugs. Practical syntheses of derivatives of this bicyclic scaffold were developed, based on [3 + 2] cycloaddition of the ylide generated from N-benzyl-1-methoxy-N-((trimethylsilyl)methyl)methanamine and 4-substituted 2,3-dihydrothiophene 1,1-dioxides. All of the 3-substituted hexahydro-2H-thieno[2,3-c]pyrrole 1,1-dioxide derivatives were obtained as single diastereomers. Conformational properties of the hexahydro-2H-thieno[2,3-c]pyrrole 1,1-dioxide derivatives were explored using X-ray diffraction studies. The potential of the scaffold to generate libraries of 3D-shaped molecules was demonstrated.     

Multi-component coupling synthesis of polycyclic pyrrole derivatives via Ir- and Rh-catalyzed cycloisomerizations with microwave heating

CuBr₂-catalyzed three-component coupling of N-benzylallylamine, ethyl glyoxalate, and terminal alkynes afforded glycinate-tethered 1,6-enynes, which were further transformed into polycyclic pyrrole-2-carboxylates via iridium-catalyzed cycloisomerization/Diels-Alder cycloaddition/dehydrogenation sequence under conventional and microwave heating conditions. The corresponding β-amino acid analogues were obtained from the Ir-catalyzed reaction of enynes prepared from lithium amides of allylamines with methyl non-2-en-4-ynoate. The Cu-catalyzed Mannich-type condensation was further extended to the synthesis of the glycinate-tethered dienyne and cyclopropylenyne, which were subjected to Rh-catalyzed cycloisomerizations to furnish bicyclic amino acids.