Unsubstituted Pyrrole Research Articles

Multiple C–C Bond Cleavage Reactions Catalyzed by Tolyporphin Tetrapyrrole Biosynthetic Enzymes

Tolyporphin A is an unusual tetrapyrrole secondary metabolite containing pendant deoxysugars and unsubstituted pyrrole β sites. Herein, we describe the biosynthesis of the tolyporphin aglycon core. HemF1 catalyzes the oxidative decarboxylation of two propionate side chains of coproporphyrinogen III, an intermediate in heme biosynthesis. HemF2 then processes the two remaining propionate groups to generate a tetravinyl intermediate. All four vinyl groups from the macrocycle are truncated by TolI via repeated C-C bond cleavages to generate the unsubstituted pyrrole β sites of tolyporphins. This study illustrates how the unprecedented C-C bond cleavage reactions branch from canonical heme biosynthesis to produce tolyporphins.

The mechanism of electrophilic addition of singlet oxygen to pyrrolic ring

Pyrrolic compounds assume an important role in the chemistry of living organisms, coal surrogates and novel drugs. However, literature reports a few studies on their reactivity towards prominent oxidising agents. This contribution presents a comprehensive mechanistic study of the oxidation of unsubstituted pyrrole with singlet oxygen (O2 1∆g) by deploying a quantum chemical framework leading to the production of succinimide, as the major products, through a Diels–Alder addition of O2 1∆g to the aromatic ring. Other products such as maleimide, hydroperoxide, formamide and epoxide adducts appear to form via insignificant channels. The primary Diels–Alder channel encompasses a barrier of 41 kJ/mol with a fitted rate constant of k(T) = 1.87 × 10−13 exp(− 48,000/RT) cm3 mol−1 s−1. Furthermore, a kinetic study has been undertaken to investigate the influence of substituents on reaction rate of the Diels–Alder addition of singlet oxygen to a pyrrolic ring. The results clarify that electropositive substituents such as BeH and BH2 operate as π-acceptors and thus deactivate the ring towards electrophilic attack of singlet oxygen. However, substituents comprising of strong π-donors, e.g., NH2 and OH, destabilise the ring structure, increasing its oxidation reactivity.

Pyrroles as Dienes in (4+3) Cycloadditions

This short review summarizes the examples to date of successful (4+3) cycloadditions, including formal (4+3) cycloadditions, where pyrrole derivatives reacted as the diene component, to provide aza-bridged bicyclic and polycyclic adducts.1 Introduction2 Unsubstituted Pyrroles as Dienes in (4+3) Cycloadditions3 C-Substituted Pyrroles as Dienes in (4+3) Cycloadditions4 Intramolecular Pyrrole (4+3) Cycloadditions5 Conclusions

Carbazoles and Hydrazone‐Bridged Thiazole‐Pyrrole Derivatives as New Inhibitors of α‐Glucosidase

AbstractCarbazoles and hydrazone‐bridged thiazole‐pyrrole derivatives are known to exhibit a wide range of biological activities including antimicrobial activity. This work is a further extension of their biological activities that identifies a total of 13 of these derivatives as new α‐glucosidase inhibitors. The carbazole derivatives exhibited noncompetitive inhibition of the enzyme with the inhibitor possessing the 2‐benzoimidazole substitution being the most potent in the series. Compounds possessing the 2‐benzothiazole, 2‐benzoxazole and quinoline groups were also found to be promising for enzyme inhibition. The hydrazone‐bridged thiazole‐pyrrole derivatives showed competitive enzyme inhibition with a number of groups responsible for potent enzyme inhibition including 4‐nitrophenyl, 4‐bromophenyl, and 4‐methoxyphenyl groups. Moreover, the hydrazone derivatives with unsubstituted pyrrole ring were found to be more favorable to α‐glucosidase inhibition than the ones possessing the methyl‐substituted ring. The current work may provide new structural and functional diversity to drug discovery of promising α‐glucosidase inhibitors as anti‐diabetic drugs.

An alternative synthesis of benziporphyrins starting from isophthaloyl chloride

An alternative route to benziporphyrins has been developed. Reaction of an [Formula: see text]-unsubstituted pyrrole ethyl ester with isophthaloyl chloride in the presence of aluminum chloride afforded a diketone that underwent selective reduction with diborane to give a benzitripyrrane. Cleavage of the ethyl esters with sodium hydroxide in refluxing ethylene glycol, followed by acid catalyzed condensation with a pyrrole dialdehyde and oxidation with DDQ, generated the targeted benziporphyrin product. Spectrophotometric titration of the benziporphyrin with trifluoroacetic acid (TFA) demonstrated the sequential formation of mono- and dicationic species. At lower dilutions, the free base benziporphyrin showed unusually strong [Formula: see text] coupling between two adjacent methyl substituents, indicating that the connecting unit has substantial olefinic characteristics.

Unprecedented α-substituted BOPHY dyes via a key 3,8-dichloroBOPHY intermediate

We present a high-yielding synthesis for 3,8-dichloroBOPHY. Starting from unsubstituted pyrrole, this α-halogenated fluorophore was obtained in 51% yield. Subsequent functionalization via nucleophilic substitutions with O, N and S-nucleophiles was achieved in yields up to 88%. Stille and Sonogashira coupling reactions led to red-shifted chromophores. The absorption maxima of the synthesized dyes vary from 442 to 545 nm, with emission maxima ranging from 474 to 612 nm and quantum yields of fluorescence in solution from <1% to 100%.

Synthesis and Cycloaddition Reactions of Stabilized Münchnones

A family of stabilized münchnones bearing an acyl group at C4 have been prepared and studied in alkyne cycloaddition reactions. These reactions are highly regioselective, and the method represents a rapid and straightforward route to densely substituted pyrroles. Finally, the C4‐stabilizing units can be further manipulated to furnish carboxylic acid and amide groups, or removed altogether to provide unsubstituted pyrroles.

ChemInform Abstract: Iridium‐Catalyzed Methylation of Indoles and Pyrroles Using Methanol as Feedstock.

AbstractWhile indoles are regioselectively mono‐methylated at C‐3, pyrroles give mixtures of mono‐, di‐, and (in the case of unsubstituted pyrrole) polymethylated products.

Green synthesis of dipyrromethanes in aqueous media catalyzed by SO3H-functionalized ionic liquid.

A mild, efficient and metal-free method was described for the green synthesis of dipyrromethanes from aldehydes and unsubstituted pyrrole catalyzed by SO3H-functionalized ionic liquids (SO3H-ILs) in aqueous media at room temperature. Notably, SO3H-ILs, 1-butylsulfonic-3-methylimidazolium hydrogen sulfate ([bsmim][HSO4]) was the most efficient catalyst for moderate to good yields of the corresponding desired products.

Platinum‐Catalyzed Domino Reaction with Benziodoxole Reagents for Accessing Benzene‐Alkynylated Indoles

AbstractIndoles are omnipresent in natural products, bioactive molecules, and organic materials. Consequently, their synthesis or functionalization are important fields of research in organic chemistry. Most works focus on installation or modification of the pyrrole ring. To access benzene‐ring‐functionalized indoles with an unsubstituted pyrrole ring remains more challenging. Reported herein is a platinum‐catalyzed cyclization/alkynylation domino process to selectively obtain C5‐ or C6‐functionalized indoles starting from easily available pyrroles. The work combines, for the first time, a platinum catalyst with ethynylbenziodoxole hypervalent iodine reagents in a domino process for the synthesis of polyfunctionalized arene rings and gives access to important building blocks for the synthesis of bioactive compounds and organic materials.

Platinum-catalyzed domino reaction with benziodoxole reagents for accessing benzene-alkynylated indoles.

Indoles are omnipresent in natural products, bioactive molecules, and organic materials. Consequently, their synthesis or functionalization are important fields of research in organic chemistry. Most works focus on installation or modification of the pyrrole ring. To access benzene-ring-functionalized indoles with an unsubstituted pyrrole ring remains more challenging. Reported herein is a platinum-catalyzed cyclization/alkynylation domino process to selectively obtain C5- or C6-functionalized indoles starting from easily available pyrroles. The work combines, for the first time, a platinum catalyst with ethynylbenziodoxole hypervalent iodine reagents in a domino process for the synthesis of polyfunctionalized arene rings and gives access to important building blocks for the synthesis of bioactive compounds and organic materials.

Potency of photoinduced electron transfer and antioxidant efficacy of pyrrole and pyridine based Cu(II)-Schiff complexes while binding with CT-DNA

Here we report a systematic and comparative study to define a correlation between the structure and function of a series of simple, biologically active small inorganic Schiff base copper complexes for the occurrence of charge transfer phenomenon in calf thymus DNA (CT-DNA) using transient absorption spectroscopy corroborated with magnetic field effect. Four copper(II) Schiff base complexes with differently substituted heterocyclic ligands with antioxidant activity have been used. The binding constants of the order of ∼104 support the moderate binding affinity of the complexes towards CT-DNA. The methyl-substituted pyrrole complex shows maximum binding affinity (Kb: 8.33×104) compared to others. The occurrence of photoinduced electron transfer (PET) from CT-DNA to pyrrole containing complexes has been confirmed by identifying the corresponding transient radical ions whereas the extent of PET with pyridine substituted complexes is too small to be observed. The increase of the yield of radical ions in presence of magnetic field depicts that the initial spin correlation in geminate radical ion pair is triplet. The difference between experimental and calculated B½ values, the measure of hyperfine interactions (HFI) present in the system, arises due to hole hopping through intrastrand and interstrand DNA bases. The unsubstituted pyrrole complexes cleave DNA much more than the methyl-substituted one. Therefore, the probability of intrastrand superexchange increases with methyl-substituted complexes, that reduces the rate of hole hopping and hence the B½ value.

The Dual Role of Ruthenium and Alkali Base Catalysts in Enabling a Conceptually New Shortcut to N-Unsubstituted Pyrroles through Unmasked α-Amino Aldehydes

A virtually salt-free and straightforward bimolecular assembly giving N-unsubstituted pyrroles through fully unmasked α-amino aldehydes, which was enabled by the dual effects of a catalytic ruthenium complex and an alkali metal base, is reported. Either solvent-free or acceptorless dehydrogenation facilitates high atom, step, and pot economy, which are otherwise difficult to achieve in multistep operations involving protection/deprotection.

Expedient one-step synthesis of nitrogen stilbene analogs by transition metal-free hydroamination of arylacetylenes with pyrroles

A novel family of nitrogen stilbene analogs, 1-styrylpyrroles, has been synthesized in good to excellent yields by a straightforward facile transition metal-free addition of pyrroles to arylacetylenes in the KOH/DMSO system (90–120°C, 5–13h). Thermodynamically controlled E/Z-isomer ratio of 1-styrylpyrroles depends on structure of both pyrroles and acetylenes ranging from ca. 100% E-stereoselectivity (for the pair unsubstituted pyrrole—phenylacetylene) to 90, 96% Z-stereoselectivity (for the pairs: 2-phenylpyrrole—phenylacetylene and 2-(2-thienyl)pyrrole—phenylacetylene, respectively).

Synthesis and biological evaluation of new N-alkyl 1-aryl-5-(1 H-pyrrol-1-yl)-1 H-pyrazole-3-carboxamides as cannabinoid receptor ligands

A series of N-alkyl 1-aryl-5-(1 H-pyrrol-1-yl)-1 H-pyrazole-3-carboxamides were synthesized as new ligands of the human recombinant receptor hCB 1. n-Alkyl carboxamides brought out different SARs from the branched subgroup. Unsubstituted pyrrole derivatives bearing a tert-alkyl chain at the 3-carboxamide nitrogen showed greater hCB 1 receptor affinity than the corresponding unbranched compounds. In particular, the tert-butyl group as a chain terminal moiety strongly improved hCB 1 receptor affinity (compound 24: K i = 45.6 nM; 29: K i = 37.5 nM). Acute administration of either compound 12 or 29 resulted in a specific, dose-dependent reduction in food intake in rats. Such results provide an useful basis for the design of new CB 1 ligands.

Effects of Perfluorination on Thiophene and Pyrrole Oligomers

The effect of perfluorination on thiophene and pyrrole oligomers in neutral, cationic, and anionic states was investigated with density functional theory at the (TD)B3P86-30%/6-31G* level. For the title compounds fluorination leads to planarization. For pyrroles a band gap reduction of 0.58 eV results, as unsubstituted pyrroles are nonplanar and disordered in the solid state. For thiophene the band gap is slightly increased as long thiophene oligomers are almost planar. Ionization energies and electron affinities increase upon fluorination by 0.65 and 0.60 eV for polythiophene and by 0.45 and 0.90 eV for polypyrrole. Conduction band widths increase by 0.5 for polythiophene and by 0.7 eV for polypyrrole. Spectra of charged (doped) forms are almost identical to those of the parent systems. Like parent systems, fluorinated oligomers with chain lengths of more than six rings develop a third UV absorption that increases in strength and decreases in energy upon chain length increase.

Pyrrolamidocalix[4]arenes: new receptors for anion recognition

Pyrrolamidocalix[4]arenes 1– 4, members of a new class of anion receptors bearing pyrrolic units at the upper rim of calix[4]arene macrocycle, have been readily synthesized in good yields. Derivatives 1 and 3, with unsubstituted pyrrole units, show a good selectivity for H 2 PO 4 - over F − and AcO −, while the presence of electron-withdrawing NO 2 substituents in 2 and 4 inverts the selectivity favoring more basic AcO − and F −. In addition, it is demonstrated that the flexibility of calix[4]arene skeleton, present in 1 but absent in 3, is very important in the fitting process that leads the amidopyrrole moieties to wrap the tetrahedral H 2 PO 4 - guest.

N → C2 → C3 migration of the dichlorophosphino group in the synthesis of phosphorylated NH‐pyrroles

AbstractA successive N → C2 → C3 migration of the dichlorophosphino group has been found to occur in phosphorylation of unsubstituted pyrrole with phosphorus trichloride. As a result of this migration, a number of hitherto unknown C‐phosphorylated N‐unsubstituted pyrroles have been obtained. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:671–676, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20495

New shells for magnetic nanoparticles based on polypyrrole functionalized with α-amino acids

New functionalized magnetic core-shell nanostructures were developed based on magnetite as magnetic core covered with pyrrole copolymers substituted by α-amino acids. The 3-substituted pyrrole monomers were synthesized by amide formation between an α-amino acid and 4-(1phenylsulfonyl-(1H-pyrrol-3-yl)-4-oxo-butyric acid. Further, these substituted pyrrole monomers were copolymerized with unsubstituted pyrrole by oxidation with ammonium persulfate in the presence of water based magnetic nanofluids yielding functionalized magnetic core-shell nanostructures. The morphology of these magnetic functionalized polypyrrole core-shell nanoparticles was investigated by TEM and HRTEM, while the molecular structures and magnetic properties were investigated by FTIR spectroscopy and magnetization measurements, respectively.

Conducting Polymers Based on Alkylthiopyrroles

Three 3,4-bis(alkylthio)pyrroles (5a−c) were synthesized by a nonclassical pyrrole ring formation reaction followed by alkylation of the dithiol-2-one functional group. UV−vis absorption studies together with time dependent density-functional theory (TD-DFT) computations suggest that the monomers (5a−c) display low-energy π−σ* transitions (5a, 254 nm; 5b, 232 nm; 5c, 240 nm) compared to pyrrole (208 nm). Cyclic voltammetry investigations show that the monomers 5a−c possess significantly lower oxidation potentials (0.60 V for 5a, 0.58 V for 5b, and 0.71 V for 5c) than unsubstituted pyrrole (1.0 V). The corresponding polymers were successfully prepared by anodic electropolymerization and/or chemical oxidation (FeCl3 as oxidant) and investigated by cyclic voltammetry, spectroelectrochemistry and in situ conductivity studies. Our investigations of monomeric 3,4-disubstituted pyrroles and corresponding polymers suggest that the electron donating alkylthio substituents at the 3- and 4-positions of the pyrrole r...