Heterocyclic Subunits Research Articles

Electrochemical Generation of Nitrogen‐centered Radicals and its Application for the Green Synthesis of Heterocycles

AbstractElectrochemistry became a unique and powerful tool for the preparation of a plethora of valuable chemical species including functional materials, drug candidates and clinically approved pharmaceuticals. Organic electrosynthesis well satisfies main goals of green chemistry development and is considered as one of the useful approaches toward the creation of sustainable future. Since nitrogen heterocyclic scaffolds still retain their importance for the construction of novel materials and medications, one of the emerging trends in organic electrochemistry is the discovery of novel green and sustainable synthetic methods toward the assembly of heterocyclic subunits. In this regard, organic electrochemistry provides an efficient platform for environmentally benign generation of various nitrogen‐centered radicals which are prominent intermediates in the synthesis of nitrogen heterocycles. In this Review, recent developments in the creation of green synthetic methods for the construction of nitrogen heterocycles via electrochemical generation of nitrogen‐centered radicals are summarized. The special emphasis is devoted to the influence of solvent, electrodes and electrolytes on the electrochemical step, since these crucial parameters regulate the process efficiency.

Two Acridone Units in One Crown Ether

We present here a critical overview on the effects of the second heterocyclic subunit in a bisacridino-crown ether by the discussion of its role in modulating optochemical behavior and preference in molecular recognition. The preparation of a new bisacridono-crown ether is presented including synthetic difficulties, and its fluorescence properties and selectivity in formation of inclusion complexes with various cations are evaluated in the light of reported analogues.

Novel family of nitrogen-rich energetic (1,2,4-triazolyl) furoxan salts with balanced performance.

Nitrogen-rich energetic materials comprised of a combination of several heterocyclic subunits retain their leading position in the field of materials science. In this regard, a preparation of novel high-energy materials with balanced set of physicochemical properties is highly desired. Herein, we report the synthesis of a new series of energetic salts incorporating a (1,2,4-triazolyl) furoxan core and complete evaluation of their energetic properties. All target energetic materials were well characterized with IR and multinuclear NMR spectroscopy and elemental analysis, while compound 6 was further characterized by single-crystal X-ray diffraction study. Prepared nitrogen-rich salts have high thermal stability (up to 232°C), good experimental densities (up to 1.80 g cm−3) and high positive enthalpies of formation (344–1,095 kJ mol−1). As a result, synthesized energetic salts have good detonation performance (D = 7.0–8.4 km s−1; p = 22–32 GPa), while their sensitivities to impact and friction are quite low.

An Updated Review on the Synthesis and Antibacterial Activity of Molecular Hybrids and Conjugates Bearing Imidazole Moiety.

The rapid growth of serious infections caused by antibiotic resistant bacteria, especially the nosocomial ESKAPE pathogens, has been acknowledged by Governments and scientists and is one of the world’s major health problems. Various strategies have been and are currently investigated and developed to reduce and/or delay the bacterial resistance. One of these strategies regards the design and development of antimicrobial hybrids and conjugates. This unprecedented critical review, in which our continuing interest in the synthesis and evaluation of the bioactivity of imidazole derivatives is testified, aims to summarise and comment on the results obtained from the end of the 1900s until February 2020 in studies conducted by numerous international research groups on the synthesis and evaluation of the antibacterial properties of imidazole-based molecular hybrids and conjugates in which the pharmacophoric constituents of these compounds are directly covalently linked or connected through a linker or spacer. In this review, significant attention was paid to summarise the strategies used to overcome the antibiotic resistance of pathogens whose infections are difficult to treat with conventional antibiotics. However, it does not include literature data on the synthesis and evaluation of the bioactivity of hybrids and conjugates in which an imidazole moiety is fused with a carbo- or heterocyclic subunit.

A controlled blue-shift in meso-nitrogen aryl fused DIPY and BODIPY skeletons

An aryl-amine attached to the meso-position of the BODIPY skeleton quenches the fluorescence. The observed edge fusion creates a new heterocyclic subunit simultaneously increasing the efficiency of emission. The quantitative deprotonation of meso NH functionality leads to absorbance blue shift and increased emission quantum yield showing potential for formation of BODIPY based changeable chromophores.

Phyllostictine A: total synthesis, structural verification and determination of substructure responsible for plant growth inhibition.

The first total synthesis of phyllostictine A (PA) is reported, which confirms the structure of this fungal metabolite and its (6S,7R,8S)-stereochemistry. Both synthetic PA and an analogue containing the 5-methylene-1,5-dihydro-2H-pyrrol-2-one nucleus exhibit μM inhibitory activity in root growth assays against Arabidopsis thaliana, indicating that this heterocyclic subunit is key to the herbicidal activity of the natural product.

Up Scaling Strategies to Improve the Industrial Production of Bacitracin at Largescale.

Bacitracin was discovered and named after a 7 year old American girl, Margaret Tracey in 1943 as Bacillus was isolated from her wounds. Bacillus licheniformis is usually present in soil and bird feathers. This bacterium is most commonly present around back plumage and chest of birds. There are different types of bacitracin but the one most potent is Bacitracin A. Bacitracin induced proteins are localized in bacterial membrane. Production of antibiotic initially stopped, resumed by induction of bacitracin induced protein but after few mitotic divisions microbes reverted to their vulnerable state. Induction of protein ceases after 4th hour of stationary phase. Immobilization is necessary for economic, process convenience and stability of the cell. Moreover, immobilization increases the ability of the cell to produce product in high quantity. Maximum production of antibiotic was noted at pH 8 after 4 hours of incubation at various glucose concentrations in shake flask fermentation at 30°C when immobilized in polyacrylamide gel. Increase in antibiotic activity was also found with increase in use of cells. Efforts have been made to alter heterocyclic metal binding subunit of bacitracin by synthesizing heterocyclic building blocks that can be coupled to linear decapeptide and consequently cyclization by PCPTE biodomain of bacitracin. Derivatives of bacitracin showed antimicrobial activities indicating the possibility of overcoming existing limitations just by altering their heterocyclic subunit. Bioactivity and stability can be increased by modifying peptide backbone of compounds.

Synthesis of N,N‐Dialkylamino‐nor‐Dihydroxanthene‐Hemicyanine Fused Near‐Infrared Fluorophores and Their First Water‐Soluble and/or Bioconjugatable Analogues

The effective synthesis of extended conjugated N,N-dialkylamino-nor-dihydroxanthene-based fluorophores is described from diversely functionalized salicylic aldehydes. The access to these original fluorescent derivatives proceeded in two steps through a one-pot construction of the unusual nor-dihydroxanthene (nor-DHX) scaffold followed by a diversification step providing a wide variety of nor-DHX-hemicyanine fused dyes emitting in the range of 730-790 nm. The versatility of our approach has enabled a further extension to the late-stage introduction of negatively/positively charged polar groups onto their terminal nitrogen heterocyclic subunit, thereby giving access to the first water-soluble and/or bioconjugatable members of this emerging class of NIR fluorophores. Our water-solubilizing method is easily implementable, and the nor-DHX-hemicyanine skeleton maintains satisfying fluorescence quantum yields (5-20 %) under physiological conditions. Finally, the bioconjugation ability of fluorescent derivatives bearing a free carboxylic acid was demonstrated through the covalent labeling of a model protein, namely, bovine serum albumin.

The synthesis of cardenolide and bufadienolide aglycones, and related steroids bearing a heterocyclic subunit.

Covering: early studies through to March 2016Cardenolides and bufadienolides constitute an attractive class of biologically active steroid derivatives which have been used for the treatment of heart disease in traditional remedies as well as in modern medicinal therapy. Due to their application as therapeutic agents and their unique molecular structures, bearing unsaturated 5- or 6-membered lactones (or other heterocycles) attached to the steroid core, cardio-active steroids have received great attention, which has intensified during the last decade, in the synthetic organic community. Advances in the field of cross-coupling reactions have provided a powerful tool for the attachment of lactone subunits to the steroid core. This current review covers a methodological analysis of synthetic efforts to cardenolide and bufadienolide aglycones. Special emphasis is given to cross-coupling reactions applied for the attachment of lactone subunits at sterically very hindered positions of the steroid core. The carefully selected partial and total syntheses of representative cardio-active steroids will also be presented to exemplify recent achievements (improvements) in the field.

ChemInform Abstract: Structure Modification and Spectroscopic Properties of Artificial Porphyrinoids

AbstractReview: 48 refs.

Reversal of enantioselectivity induced by the achiral part of an organocatalyst in a Diels–Alder reaction

A new series of chiral organocatalysts was developed by attaching achiral heterocyclic units via a methylene group to (S)-2-hydroxyethylbenzimidazole for the asymmetric Diels–Alder reaction between anthrone enolate and maleimides. While organocatalysts with pyridine, quinoline, and 1,3,4-oxadiazole achiral heterocyclic subunits gave Diels–Alder adducts with an (S,S)-configuration, the organocatalyst with a benzotriazole subunit caused formation of the (R,R)-configuration for the Diels–Alder adducts

ChemInform Abstract: 10‐Step Asymmetric Total Synthesis and Stereochemical Elucidation of (+)‐Dragmacidin D.

The asymmetric synthesis of dragmacidin D (1) was completed in 10 steps. Its sole stereocenter was set by using direct asymmetric alkylation enabled by a C2-symmetric tetramine and lithium N-(trimethylsilyl)-tert-butylamide as the enolization reagent. A central Larock indole synthesis was employed in a convergent assembly of the heterocyclic subunits. The stereochemical evidence from this work strongly supports the predicted S configuration at the 6′′′ position, which is consistent with other members of the dragmacidin family of natural products.

Structure Modification and Spectroscopic Properties of Artificial Porphyrinoids

AbstractIn this review article, we summarize our recent progress in rational structure modification and spectroscopic studies of artificial porphyrinoids. Structural modifications, including meso aryl substitution, peripheral aromatic ring fusion, ring contraction and expansion, and core modification with heterocyclic subunits other than pyrrole, perturb the electronic structures and aromaticity of porphyrinoids, thus regulating their electronic properties. The relationship between structure and spectroscopic properties as well as the applications of these porphyrinoids are also reviewed.

10‐Step Asymmetric Total Synthesis and Stereochemical Elucidation of (+)‐Dragmacidin D

AbstractThe asymmetric synthesis of dragmacidin D (1) was completed in 10 steps. Its sole stereocenter was set by using direct asymmetric alkylation enabled by a C2‐symmetric tetramine and lithium N‐(trimethylsilyl)‐tert‐butylamide as the enolization reagent. A central Larock indole synthesis was employed in a convergent assembly of the heterocyclic subunits. The stereochemical evidence from this work strongly supports the predicted S configuration at the 6′′′ position, which is consistent with other members of the dragmacidin family of natural products.

10-Step Asymmetric Total Synthesis and Stereochemical Elucidation of (+)-Dragmacidin D.

The asymmetric synthesis of dragmacidin D (1) was completed in 10 steps. Its sole stereocenter was set by using direct asymmetric alkylation enabled by a C2-symmetric tetramine and lithium N-(trimethylsilyl)-tert-butylamide as the enolization reagent. A central Larock indole synthesis was employed in a convergent assembly of the heterocyclic subunits. The stereochemical evidence from this work strongly supports the predicted S configuration at the 6''' position, which is consistent with other members of the dragmacidin family of natural products.

ChemInform Abstract: Acid‐Mediated Coupling of γ‐Hydroxybutenolides and Aldehydes: Synthesis of a New Class of Spirocyclic Ketal—Lactones.

AbstractThe γ‐methyl‐γ‐hydroxybutenolide (I) reacts via the intermediacy of the known molecule protoanemonin (VI) with aromatic aldehydes under conditions A) to produce spirocyclic ketal—lactones as heterocyclic subunits.

Aminonaphthalimide-based dipodal imidazolium/triazole receptors for fluorescent sensing of nucleoside polyphosphates

Novel aminonaphthalimide-based two-armed imidazolium/triazole receptors were synthesized to compare their fluorescent responses towards nucleoside polyphosphates with those of three-armed podands described recently. Our two constitutional isomer ligands comprised one imidazolium and an additional 1,2,3-triazole moiety in the binding site exhibited ‘turn-on’ fluorescence enhancements in HEPES buffer (pH 7.5) upon addition of ATP, GTP and UTP. The sensitivity of sensing was found to strongly depend on the order of heterocyclic subunits in the arms, when the imidazolium group was displaced to the vicinity of the naphthalimide marker significantly higher sensitivity was achieved. In aqueous solutions, however, the association constants were considered to be unreliable due to the occurrence of some colloidal precipitate (unvisible to the naked eye) that could be detected only by light scattering. The spectroscopic measurements repeated in HEPES–acetonitrile mixed solvent affording stable solutions gave association constants log K=6.3–6.5 for ATP, GTP and UTP alike (1:2 ligand–triphosphate stoichiometry) retaining the selectivity over di-and monophosphates.

X-ray structure and properties of a cyclo[6]pyrrole[3]thiophene

A new member of the cyclo[n]pyrrole class of expanded porphyrins was prepared from the corresponding thiophene-containing terpyrrole precursor through use of a mild electrochemical oxidative procedure. The isolated macrocycle, featuring nine heterocyclic subunits directly connected through their α,α′-positions, is the largest cyclo[n]pyrrole derivative reported to date. The structure obtained via synchrotron radiation-based studies revealed a dimeric arrangement involving individual macrocyclic subunits.

Electrochemical Synthesis of a Thiophene‐Containing Cyclo[9]pyrrole

A new member of the cyclo[n]pyrrole class of expanded porphyrins could be prepared from the corresponding thiophene-containing terpyrrole precursor through use of a mild electrochemical oxidative procedure. The isolated macrocycle, featuring nine heterocyclic subunits directly connected through their α,α'-positions, is the largest cyclo[n]pyrrole derivative reported to date (see figure).

Capillary electrophoresis profiles and fluorophore components of humic acids in Nebraska corn and Philippine rice soils

As humic substances represent relatively high molecular mass polyelectrolytes containing aromatic, aliphatic and heterocyclic subunits, capillary electrophoresis (CE) has become an attractive method for “finger-print” characterization of humic acids. In addition, fluorescence excitation-emission matrix (EEM) spectroscopy is also a highly sensitive analytical method, providing information on flurophore properties of humic acids. However, basic information on the CE profile patterns and fluorophore components of humic acid fractions from different agricultural soils is rare. Consequently, we sequentially extracted the mobile humic acid (MHA) and recalcitrant Ca humate (CaHA) fractions from Nebraska corn soils and Philippine rice soils under different fertilization schemes, and acquired their CE profiles and fluorophore component composition. We observed greater differences in the CE profiles between soils than between management practices on the same soil, reflecting the distinct “finger-print” CE features of these soil humic fractions. Modeling analysis of EEM data indicated that four fluorophore components were present in these humic fractions. Whereas three have previously been reported in literature, we propose the features of the unknown component as being relevant to agricultural humic fractions. UV irradiation seemed to impact the Nebraska soils by disaggregating the humic fractions into their structural subunits, while impacting the Philippine soils by altering the functional groups of humic fractions. This research provides insight into the CE profiles and fluorophore features of humic acid fractions from different agricultural soils.