Carbon-hetero Bonds Research Articles

Synthesis and BSA binding study of the Cu(II) complex and applications of it to enhance catalytic activity for C(Sp2)-H bond functionalization and for the synthesis of polyhydroquinolines

Among the various copper-catalyzed coupling reactions, C–S and C–N bond-forming reactions have carried off plentiful recognition due to their demand in the synthesis of molecules having biological and pharmaceutical impact. Organo-copper complex has an incontestable supremacy over the other catalytic complex due to its low cost and the use of readily accessible and stable ligands. As a consequence and in continuation of our explorative studies in this direction, an efficient and novel organo-copper complex has been synthesized and characterized by spectroscopic (NMR, FT-IR) and single crystal X-ray diffraction (XRD) methods. The synthesized stable metal complex has fascinating physical, chemical, biological and catalytic properties. In the chemical exploration refer to protein-metal interactions; we have often used Bovine Serum Albumin (BSA) protein. The synthesized copper complex has the potential to form coordinate bonds with functional groups present in BSA, together with amino acid residues and the protein backbone. The binding of metal complexes to BSA has outstanding imputation in medicinal chemistry. For enhancement of the catalytic activity of the organo-copper complex, we have evaluated it in carbon-hetero bond formation reactions where it proffered an influential tool for the establishment of C–S and C–N bonds.

Recent Advances in Hypervalent Iodine Reagents and m-CPBA Mediated Oxidative Transformations

Abstract: Among the several peroxides available, meta-chloroperbenzoic acid (mCPBA) plays an efficient role of oxidizing reagent and is used for many oxidative transformations, such as oxidation of various functional groups, carbon-carbon, carbon-hetero bond formation, heterocyclic ring formation, heteroarylation, oxidative cross-coupling, lactonization, oxidative dearomatization, α-oxytosylation or α-acetoxylation, oxidative C-C bond activation and in other miscellaneous reactions. The purpose of this review is to critically discuss the significant contributions of mCPBA along with hypervalent iodine/iodine reagents in organic synthesis from mid-2015 to date.

Photocatalytic decarboxylation of free carboxylic acids and their functionalization.

Visible light mediated decarboxylative functionalization of carboxylic acids and their derivatives has recently emerged as a novel and powerful toolkit for small molecule activation in diverse carbon-carbon and carbon-hetero bond forming reactions. Naturally abundant highly functionalized bench-stable carboxylic acid analogs have been employed as promising alternatives to non-trivial organometallic reagents for mild and eco-benign synthetic transformation with traceless CO2 by-products. In this highlight article, we focus on the development of various photodecarboxylative functionalization strategies along with intra/inter-molecular cyclization via concerted single electron transfer (SET) or energy transfer (ET) pathways. Moreover, widely explored carboxylic acids are systematically classified here into four categories; i.e., α-keto, aliphatic, α,β-unsaturated, and aromatic analogs for a concise overview to the readership. The association of decarboxylative radical species with coupling partners to construct C-C and C-N/O/S/P/X bonds for each analogous acid has been presented in brief.

Dearomatization of α-Unsubstituted β-Naphthols

AbstractThis Account summarizes the highly appealing dearomatization reactions of β-naphthols for the synthesis of highly functionalized, three-dimensional structures starting with simple planar aromatic compounds. The reactions are categorized mainly from the viewpoint of the construction of carbon–hydrogen, carbon–carbon, and carbon–hetero bonds (C–N/O, C–Cl, C–F) at the α-position of β-naphthols. The dearomatized products play an important role in organic synthesis and materials science.1 Introduction2 Construction of Carbon–Hydrogen Bonds at the α-Position of β-Naphthols3 Construction of Carbon–Carbon Bonds at the α-Position of β-Naphthols4 Construction of Carbon–Nitrogen/Oxygen Double Bond at the α-Position of β-Naphthols5 Construction of Carbon–Carbon and Carbon–Oxygen Bonds at the α-Position of β-Naphthols6 Construction of Carbon–Halogen Bonds at the α-Position of β-Naphthols7 Conclusion

Pro-aromaticity Enabled Dealkenylative Functionalizations via Photo-Excitation and Oxidation.

A general and practical approach for diverse dealkenylative functionalization of olefin-containing substrates has been developed through the one-pot formation and utilization of pro-aromatic 1,4-dihydropyridazines using tetrazine as the key cycloaddition reagent. Triggered by either excitation or oxidation, the targeted C-C bonds in the 1,4-dihydropyridazine intermediates could be readily cleaved to generate alkyl radicals for subsequent transformations. Diverse carbon-carbon and carbon-hetero bond forming protocols, including Giese-type addition, hydrazination, borylation, Minisci-type alkylation, copper-catalyzed NH alkylation, acylation, alkynylation, cyanation, and azidation, are achieved in a highly modular fashion.

Synthesis of antiviral drugs by using carbon–carbon and carbon–heteroatom bond formation under greener conditions

Abstract Antiviral medications are a branch of medicines notably used to treat that cause many significant diseases in humans and animals. This monograph mainly focuses on recent developments and synthesis of antiviral drugs using carbon-carbon and carbon–hetero bond cross-coupling chemistry. Viral infections exact several severe human diseases, accounting for remarkably high mortality rates. In this sense, academia and the pharmaceutical industry continuously search for novel compounds with better antiviral activity. The researchers face the challenge of developing greener and economical ways to synthesize these compounds and make significant progress.

Characterizing the Relationship Between the Chemical Structures of Drugs and their Activities on Primary Cultures of Pediatric Solid Tumors

Despite continued efforts to develop new treatments, there is an urgent need to discover new drug leads to treat tumors exhibiting primary or secondary resistance to existing drugs. Cell cultures derived from patient-derived orthotopic xenografts are promising pre-clinical models to better predict drug response in cancer recurrence. The aim of the study was to investigate the relationship between the physiochemical properties of drugs and their in vitro potency as well as identifying chemical scaffolds biasedtowards selectivity or promiscuity of such drugs. The bioactivities of 158 drugs screened against cell cultures derived from 30 cancer orthotopic patient-derived xenograft (O-PDX) models were considered. Drugs were represented by physicochemical descriptors and chemical structure fingerprints. Supervised learning was employed to model the relationship between features and in vitro potency. Drugs with in vitro potency for alveolar rhabdomyosarcoma and osteosarcoma tend to have a higher number of rings, two carbon-hetero bonds and halogens. Selective and promiscuous scaffolds for these phenotypic targets were identified. Highly-predictive models of in vitro potency were obtained across these 30 targets, which can be applied to unseen molecules via a webserver (https://rnewbie.shinyapps.io/Shobek-master). It is possible to identify privileged chemical scaffolds and predict the in vitro potency of unseen molecules across these 30 targets This information and models should be helpful to select which molecules to screen against these primary cultures of pediatric solid tumors.

Aminoperoxide adducts expand the catalytic repertoire of flavin monooxygenases.

One of the hallmark reactions catalyzed by flavin-dependent enzymes is the incorporation of an oxygen atom derived from dioxygen into organic substrates. For many decades, these flavin monooxygenases were assumed to use exclusively the flavin-C4a-(hydro)peroxide as their oxygen-transferring intermediate. We demonstrate that flavoenzymes may instead employ a flavin-N5-peroxide as a soft α-nucleophile for catalysis, which enables chemistry not accessible to canonical monooxygenases. This includes, for example, the redox-neutral cleavage of carbon-hetero bonds or the dehalogenation of inert environmental pollutants via atypical oxygenations. We furthermore identify a shared structural motif for dioxygen activation and N5-functionalization, suggesting a conserved pathway that may be operative in numerous characterized and uncharacterized flavoenzymes from diverse organisms. Our findings show that overlooked flavin-N5-oxygen adducts are more widespread and may facilitate versatile chemistry, thus upending the notion that flavin monooxygenases exclusively function as nature's equivalents to organic peroxides in synthetic chemistry.

Camphor Sulfonic Acid-Catalyzed Michael Reaction of Indoles with Enones

Background: Michael addition reaction is one of the most important and widely used reactions for making carbon-carbon or carbon-hetero bonds in organic synthesis. The reaction involves a facile attack of nucleophile to enone in a conjugated manner across a carbon-carbon double bond. We herein report an expeditious camphor sulfonic acid-catalyzed Michael reaction for the synthesis of different 3-substituted indole derivatives at room temperature. This method is convenient, environmentally friendly and produces products in high yields. Method: Commercially available camphor sulfonic acid is used as organo-catalyst to activate the reaction. The newly synthesized compounds are characterized by using 1HNMR, 13C NMR and IR spectroscopy. Result: A highly substituted 3-indoyle carbonyl compounds has been synthesized in excellent yield under very mild reaction conditions. Conclusion: We developed an environmentally benign synthetic method to access novel synthesis of substituted indoles under remarkably simple and high yielding reaction. Keywords: Addition reaction, camphor sulfonic acid, enone, indoles, lewis acid, michael reaction, organo-catalysis.

Visible-light activated metal catalyst-free vicinal diazidation of olefins with sulfonium iodate(i) species.

A visible light-induced vicinal diazidation of various alkenes using stable sulfonium bis(acetoxy)iodate(i) and sodium azide as a radical precursor is described. The trimethylsulfonium [bis(azido)iodate(i)] species, intrinsically generated in situ, demonstrated unprecedented reactivity toward C[double bond, length as m-dash]C π bond-promoting selective azidation under photochemical conditions without any photoredox or metal catalyst. The visible-light stimulated diazidation reaction provides a convenient and straightforward approach to highly prevalent vicinal nitrogen scaffolds of myriad therapeutic importance.

Highly efficient mesoporous polymer supported phosphine-gold(i) complex catalysts for amination of allylic alcohols and intramolecular cyclization reactions.

A series of novel heterogeneous gold(i) catalysts were synthesized by immobilizing gold(i) complexes on ordered mesoporous polymer FDU-15 and characterized by XRD, N2 adsorption–desorption, FT-IR, TEM, EDS, etc. The catalytic activities of these catalysts were evaluated by the amination reactions of allylic alcohols. Among the catalysts investigated, FDU-(p-CF3Ph)2PAuCl (3d) was identified as the most efficient catalyst. Compared to the homogeneous catalyst, the enhanced catalytic activity of the heterogeneous gold(i) catalyst is closely related to the mesoporous structure of FDU-15. The catalytic system was suitable for a broad range of substrates and can be easily recovered and recycled at least twelve times without significant loss of catalytic activity. In addition, the catalytic performance of 3d was further examined for intramolecular cyclization for the synthesis of heterocyclic compounds.

ChemInform Abstract: The Application of Heterogeneous Visible Light Photocatalysts in Organic Synthesis

AbstractReview: 147 refs.

Unraveling the origin of splice switching activity of hemoglobin β-globin gene modulators via QSAR modeling

β-Thalassemia is a blood disease caused by a mutation in the second intron of the β-globin gene of hemoglobin that leads to abnormal hemoglobin production. Low molecular weight compounds have been proposed to modulate defective splicing by binding unwanted splicing sites, thereby restoring correct splicing. This study investigates the origin of this splice switching activity in a set of 39 active and 61,000 inactive compounds. The K-means algorithm was applied to the inactive compound points with 39 clusters, in which a point from each cluster was selected to create a balanced data set of 39 active and inactive compounds. To avoid random bias, predictive models (i.e., decision tree (DT), random forest (RF), artificial neural network (ANN), partial least squares discriminant analysis (PLS-DA) and support vector machine (SVM)) were constructed 50 times. The performances of the predictive models were statistically assessed in terms of accuracy, sensitivity, specificity and Matthews correlation coefficient (MCC). RF provided an accuracy of 89.50±13.45, sensitivity of 94.97±13.49, specificity of 84.29±22.27, and MCC of 0.80±0.25 for 10-fold CV, and it provided and accuracy of 88.00±8.55, sensitivity of 87.89±13.93, specificity of 87.51±13.75, and MCC of 0.75±0.18 for external testing. Taking advantage of the built-in feature selector of RF, a thorough analysis of feature importance was conducted. Newly identified fingerprint substructures, namely, three carbon-hetero bonds (i.e., secondary amide, tertiary amide, carboxyl derivative, carboxylic acid derivative and nitrile), carbon-carbon bonds (i.e., primary carbon, secondary carbon and alkene), aromatics (hetero N nonbasic) and carbon-hetero bond (alkyl aryl ether), may provide a better understanding of the structural variations governing the splice switching activity of the hemoglobin β-globin gene.

Ultrasound-assisted Ullmann Reaction of Alkyl and Aromatic Amines with Substituted Benzoic Acids using Copper Catalyst

Copper-catalyzed arylation of nucleophiles (Ullmann, Ullmann-Goldberg and Ullmann-Hurtley) is a useful reaction in the formation of carbon-carbon and carbon-hetero bonds. 1 – 6 However, the traditi...

Isolation, Synthesis and Biomimetic Reactions of Metalloporphyrinoids in Ionic Liquids

The tetrapyrrolic uroporphyrinogen III is the common precursor of heme, chlorophylls, bacteriochlorophylls, vitamin B12 and related porphyrinoids. Heme is a prosthetic group of many proteins such as myoglobin and hemoglobin, and enzymes such as cytochrome P450 and peroxidase. Chlorophylls and bacteriochlorophylls are the basic components involved in electron and energy transfer in photosynthesis. Cobalamine is a prosthetic group of many enzymes such as RNA reductase and methyl transferase and is involved in various rearrangement reactions. The isolation and syntheses of heme, chlorophylls, bacteriochlorophylls, cobalamines and related porphyrinoids in milder conditions including ionic liquids have been discussed. Various reactions of metalloporphyrinoid enzymes such as oxidation, reduction, dehalogenation, carbon-carbon, carbon-hetero bond formation and polymerization have been mimicked by metalloporphyrinoids in ionic liquids under different reaction conditions. The non-covalent interactions of porphyrinoids in ionic liquids in biological processes, supramolecular chemistry, photodynamic therapy and newer materials have been reviewed. The impact of ionic liquids on agriculture and environmental science has also been surveyed. Keywords: Ionic liquids, metalloporphyrinoids, biomimetic reactions, supramolecular chemistry, porphyrinoid enzymes, non-covalent interactions, synthesis, protein, enzymes, oxidation

Regioselective synthesis of bioactive heterocycles by radical cyclization

In recent years free radical cyclization has emerged as one of the versatile and simplest methodology for the construction of carbon-carbon bond in organic synthesis. In multi-step synthesis its use is significant as the key step of the synthesis involve the formation of carbon-carbon or carbon-hetero bond employing radical cyclization strategy. Regioselective synthesis of heterocycles viz. uracil, pyrone, coumarin, quinolone indole, benzofuran-annulated oxygen, nitrogen and sulfur heterocyclic compounds by tri-n-butyl tin hydride and thiol-mediated radical cyclization will be presented.