Showing papers in "Organic and Biomolecular Chemistry in 2013"
TL;DR: This review intends to summarize recent research progress in novel methodology development and application in organic synthesis, and is organized in terms of key reactive intermediates.
Abstract: In the past five years, visible-light mediated photoredox catalysis has been emerging as one of the fastest growing fields in organic chemistry because of its low cost, easy availability and environmental benignness. This review intends to summarize recent research progress in novel methodology development and application in organic synthesis, and is organized in terms of key reactive intermediates.
560 citations
TL;DR: This review provides a comprehensive overview of the construction of heterocycles using Kobayashi's silylaryl triflate aryne precursors and is organized according to the type ofheterocycle generated.
Abstract: About two decades after Kobayashi's discovery in 1983 of a very mild way of generating highly reactive aryne intermediates, the synthetic community embraced o-(trimethylsilyl)aryl triflates as convenient and versatile aryne precursors for the synthesis of carbocycles and heterocycles, as well as natural products and pharmaceutically promising drug candidates. This review provides a comprehensive overview of the construction of heterocycles using Kobayashi's silylaryl triflate aryne precursors. It is organized according to the type of heterocycle generated.
373 citations
TL;DR: In this review, recent advances involving arene diazonium salts as starting materials or active intermediates for various synthetically useful applications are summarized.
Abstract: Arene diazonium salts are common, easily prepared and highly useful intermediates in organic synthesis due to their rich reactivity and diverse transformations. In this review, recent advances involving arene diazonium salts as starting materials or active intermediates for various synthetically useful applications are summarized.
363 citations
TL;DR: Recent remarkable progress with primary amine-thioureas can successfully catalyze a diverse variety of highly enantioselective transformations providing a wide range of versatile organic compounds.
Abstract: Research disclosed since the demonstration of the first examples of primary amine-thiourea organocatalysis in 2006 has shown that primary amine-based thioureas can successfully catalyze a diverse variety of highly enantioselective transformations providing a wide range of versatile organic compounds. Recent remarkable progress with these chiral catalysts is summarized in this review.
265 citations
TL;DR: This review covers uses of bismuth catalysts since 2005 with a special emphasis on the emerging applications of such catalysts, and a selection of its most promising uses in challenging synthetic transformations.
Abstract: This review covers uses of bismuth catalysts since 2005 with a special emphasis on the emerging applications of such catalysts. Low toxicity, low catalytic loading, synergistic effects with other catalysts, and some hydrocompatibility properties confer to bismuth salts major advantages. The expanding activity in the field clearly highlights the growing potential of bismuth catalysts. The article is not a comprehensive review on bismuth catalysis but a selection of its most promising uses in challenging synthetic transformations.
172 citations
TL;DR: This manuscript describes the role of non-classical hydrogen bonds (NCHBs), specifically C-HO interactions, in modern synthetic organic transformations and points out the seminal examples where C-H···O interactions have been invoked as a key stereocontrolling element.
Abstract: This manuscript describes the role of non-classical hydrogen bonds (NCHBs), specifically C–H⋯O interactions, in modern synthetic organic transformations. Our goal is to point out the seminal examples where C–H⋯O interactions have been invoked as a key stereocontrolling element and to provide predictive value in recognizing future and/or potential C–H⋯O interactions in modern transformations.
170 citations
TL;DR: In this review, recent advances in the synthesis of aromatic nitro compounds are summarized, including the nitration of aromatic hydrocarbons, aryl boronic acids, aries halides and pseudohalides, aRYl carboxylic acids and the oxidation of aryL primary amines and azides.
Abstract: Aromatic nitro compounds are important intermediates in synthetic organic chemistry as well as in the chemical industry. Numerous useful methods for their preparation have been developed in recent years. In this review, recent advances in the synthesis of aromatic nitro compounds are summarized, including the nitration of aromatic hydrocarbons, aryl boronic acids, aryl halides and pseudohalides, aryl carboxylic acids and the oxidation of aryl primary amines and azides. Their mechanisms are discussed.
157 citations
TL;DR: Recent studies in this emerging area aimed at stimulating sulfur dioxide utilization in organic (including organometallic) chemistry thanks to the development of innocuous, bench-stable reliable SO2 donors are summarized.
Abstract: Although sulfur dioxide (SO2) has been used as a reagent for organic chemistry for more than one hundred years, being endowed with quite a distinct and varied reactivity profile, which allows the synthesis of a large range of compounds, its notorious toxicity as well as its gaseous state have impeded its frequent utilization by chemists. We summarize recent studies in this emerging area aimed at stimulating its utilization in organic (including organometallic) chemistry thanks to the development of innocuous, bench-stable reliable SO2 donors. Proof-of-concept experiments have also been recently performed in biology with the design of organic SO2 donors having controlled release profiles under physiological conditions, either active against mycobacteria or used for clarifying the role of endogenously produced SO2 in living cells.
155 citations
TL;DR: This review provides a literature overview of bioorthogonal ligation methods for protein modification, which have largely evolved over the last 15 years.
Abstract: This review provides a literature overview of bioorthogonal ligation methods for protein modification, which have largely evolved over the last 15 years. Since 1990, various new reactions have been developed that do not involve naturally occurring functional handles. Especially the development of such so-called bioorthogonal ligations has significantly contributed to our ability to selectively modify biomolecules not only in the test tube, but also in living systems.
135 citations
TL;DR: An ELF bonding analysis for the C-C bond formation along the nucleophilic addition of 2-hydroxyprop-2-yl FR 28 to methyl acrylate 35 evidences that the new C- C bond is formed by C-to-C coupling of two radical centres, which are properly characterized through the use of the Parr functions.
Abstract: A set of five DFT reactivity indices, namely, the global electrophilicity ω° and nucleophilicity N° indices, the radical Parr function P°k, and the local electrophilicity ω°k and nucleophilicity N°k indices, for the study of free radicals (FRs) are proposed. Global indices have been tested for a series of 32 FRs having electrophilic and/or nucleophilic activations. As expected, no correlation between the proposed global electrophilicity ω° and global nucleophilicity N° has been found. Analysis of the local electrophilicity ω°k and nucleophilicity N°k indices for FRs, together with analysis of the local electrophilicity ωk and nucleophilicity Nk indices for alkenes, allows for an explanation of the regio- and chemoselectivity in radical additions of FRs to alkenes. Finally, an ELF bonding analysis for the C–C bond formation along the nucleophilic addition of 2-hydroxyprop-2-yl FR 28 to methyl acrylate 35 evidences that the new C–C bond is formed by C-to-C coupling of two radical centres, which are properly characterized through the use of the Parr functions.
131 citations
TL;DR: Novel organic photoCORMs based on micelle-encapsulated unsaturated cyclic α-diketones were designed and synthesized and can be activated by visible light, have potentially low toxicity, allow the delivery of carbon monoxide to be monitored by fluorescence imaging techniques, and thus are useful tools for the study of the biological function of CO.
Abstract: Novel organic photoCORMs based on micelle-encapsulated unsaturated cyclic α-diketones were designed and synthesized. These photoCORMs can be activated by visible light, have potentially low toxicity, allow the delivery of carbon monoxide to be monitored by fluorescence imaging techniques, and thus are useful tools for the study of the biological function of CO.
TL;DR: The initial developments of trienamine catalysis for highly asymmetric Diels-Alder reactions with different dienophiles are discussed and emerging opportunities for other types of cycloadditions and cascade reactions are discussed.
Abstract: Amine catalysis, through HOMO-activating enamine and LUMO-activating iminium-ion formation, is receiving increasing attention among other organocatalytic strategies, for the activation of unmodified carbonyl compounds. Particularly, the HOMO-raising activation concept has been applied to the greatest number of asymmetric transformations through enamine, dienamine, and SOMO-activation strategies. Recently, trienamine catalysis, an extension of amine catalysis, has emerged as a powerful tool for synthetic chemists with a novel activation strategy for polyenals/polyenones. In this review article, we discuss the initial developments of trienamine catalysis for highly asymmetric Diels–Alder reactions with different dienophiles and emerging opportunities for other types of cycloadditions and cascade reactions.
TL;DR: The present Perspective article summarizes the major findings that brought the research area from the pioneering findings of the 60s to the state of the art.
Abstract: Indole is by far one of the most popular heterocyclic scaffolds in nature. The intriguing and challenging molecular architectures of polycyclic, naturally occurring indolyl compounds constitute a continuous stimulus for development in organic synthesis. The field had a formidable boom across the new millennium when catalysis started revolutionizing the chemistry of indole, providing always more convincing and sustainable solutions to the selective “decoration” of this pharmacophore. A common guideline of these approaches relies on the intrinsic overexpression of electron density of the indole core. Despite less diffusion, the “dark-side” of indole reactivity, electrophilicity, has been also elegantly documented with direct applications towards the realization of specific interatomic connections that would be difficult to obtain by means of conventional indole reactivity. The present Perspective article summarizes the major findings that brought the research area from the pioneering findings of the 60s to the state of the art.
TL;DR: The chemical behavior of cyclopropyl-substituted alkynes has been probed using the reaction conditions of ruthenium-catalyzed oxidative C-H/O-H and C- H/N-H bond functionalizations and the connectivities of the key heterocyclic products were unambiguously established by X-ray diffraction analysis.
Abstract: The chemical behavior of cyclopropyl-substituted alkynes has been probed using the reaction conditions of ruthenium-catalyzed oxidative C–H/O–H and C–H/N–H bond functionalizations. The oxidative annulations proceeded with complete conservation of all cyclopropane fragments and allowed for the one-step preparation of synthetically useful cyclopropyl-substituted isocoumarins and isoquinolones with high regioselectivities and chemical yields. The connectivities of the key heterocyclic products were unambiguously established by X-ray diffraction analysis.
TL;DR: Copper-catalyzed direct conversion of benzylic alcohols to aryl nitriles was realized using NH3(aq.) as the nitrogen source, O2 as the oxidant and TEMPO as the co-catalyst.
Abstract: Copper-catalyzed direct conversion of benzylic alcohols to aryl nitriles was realized using NH3(aq.) as the nitrogen source, O2 as the oxidant and TEMPO as the co-catalyst. Furthermore, copper-catalyzed one-pot synthesis of primary aryl amides from alcohols was also achieved.
TL;DR: A BODIPY-based dye, OBEP, has been developed to act as a mitochondrial fluorescence probe that can label swollen mitochondria resulting from different degrees of cell damage in light and resist fading even after 12 h of incubation.
Abstract: A BODIPY-based dye, OBEP, has been developed to act as a mitochondrial fluorescence probe. This dye is of high stability, low toxicity and insensitive in a pH range as wide as pH 2–10. Its uptake into mitochondria is independent of mitochondrial membrane potential in living cells. OBEP can label swollen mitochondria resulting from different degrees of cell damage in light and resist fading even after 12 h of incubation.
TL;DR: The glyconanoparticles were able to discriminate between human ( α2,6 binding) and avian (α2,3 binding) RG14 (H5N1) influenza virus highlighting the binding specificity of the trivalent α 2,6-thio-linked sialic acid ligand.
Abstract: A plasmonic bioassay for the specific detection of human influenza virus has been developed based on gold nanoparticles functionalised with a designed and synthesised thiolated trivalent α2,6-thio-linked sialic acid derivative. The glyconanoparticles consist of the thiolated trivalent α2,6-thio-linked sialic acid derivative and a thiolated polyethylene glycol (PEG) derivative self-assembled onto the gold surface. Varying ratios of the trivalent α2,6-thio-linked sialic acid ligand and the PEG ligand were used; a ratio of 25:75 was found to be optimum for the detection of human influenza virus X31 (H3N2). In the presence of the influenza virus a solution of the glyconanoparticles aggregate following the binding of the trivalent α2,6-thio-linked sialic acid ligand to the haemagglutinin on the surface of the virus. The aggregation of the glycoparticles with the influenza virus induces a colour change of the solution within 30 min. Non-purified influenza virus in allantoic fluid was successfully detected using the functionalised glyconanoparticles. A comparison between the trivalent and a monovalent α2,6-thio-linked sialic acid functionalised nanoparticles confirmed that more rapid results, with greater sensitivity, were achieved using the trivalent ligand for the detection of the X31 virus. Importantly, the glyconanoparticles were able to discriminate between human (α2,6 binding) and avian (α2,3 binding) RG14 (H5N1) influenza virus highlighting the binding specificity of the trivalent α2,6-thio-linked sialic acid ligand.
TL;DR: The highly selective chemosignaling behaviors for hydrazine by a reaction-based probe of dichlorofluorescein and resorufin acetates were investigated andHydrazine signaling in tap water was tested.
Abstract: The highly selective chemosignaling behaviors for hydrazine by a reaction-based probe of dichlorofluorescein and resorufin acetates were investigated. Hydrazinolysis of latent dichlorofluorescein and resorufin acetate fluorochromes caused prominent chromogenic and fluorescent turn-on type signals. The probes selectively detected hydrazine in the presence of commonly encountered metal ions and anions as background. Dichlorofluorescein and resorufin acetates selectively detected hydrazine with detection limits of 9.0 × 10−8 M and 8.2 × 10−7 M, respectively. Furthermore, hydrazine was selectively detected over other closely related compounds, such as hydroxylamine, ethylenediamine, and ammonia. As a possible application of the acetate probes, hydrazine signaling in tap water was tested.
TL;DR: In this review, recent advances in transition-metal-catalyzed addition reactions of C-H bonds to polar C-X (X = N, O) multiple bonds, such as aldehydes, ketones, imines, isocyanates, nitriles, isOCyanides, carbon monoxide and carbon dioxide, have undergone a rapid development in recent years.
Abstract: Chemical transformations via catalytic C–H bond activation have been established as one of the most powerful tools in organic synthetic chemistry. Transition-metal-catalyzed addition reactions of C–H bonds to polar C–X (X = N, O) multiple bonds, such as aldehydes, ketones, imines, isocyanates, nitriles, isocyanides, carbon monoxide and carbon dioxide, have undergone a rapid development in recent years. In this review, recent advances in this active area have been highlighted and their mechanisms have been discussed.
TL;DR: This review aims to highlight the diversity of self-assembled nanostructures constructed from mono-disperse synthetic building blocks; with a particular focus on their design, self- assembly, functionalization with bioactive ligands and effects thereof on the self-assembly, and possible applications.
Abstract: The regulation of recognition events in nature via dynamic and reversible self-assembly of building blocks has inspired the emergence of supramolecular architectures with similar biological activity. Synthetic molecules of diverse geometries self-assemble in water to target biological systems for applications ranging from imaging and diagnostics, through to drug delivery and tissue engineering. Many of these applications require the ability of the supramolecular system to actively recognize specific cell surface receptors. This molecular recognition is typically achieved with ligands, such as small molecules, peptides, and proteins, which are introduced either prior to or post self-assembly. Advantages of the non-covalent organization of ligands include the responsive nature of the self-assembled structures, the ease of supramolecular synthesis and the possibility to incorporate a multiple array of different ligands through pre-mixing of the building blocks. This review aims to highlight the diversity of self-assembled nanostructures constructed from mono-disperse synthetic building blocks; with a particular focus on their design, self-assembly, functionalization with bioactive ligands and effects thereof on the self-assembly, and possible applications.
TL;DR: The asymmetric catalytic aza-Morita-Baylis-Hillman (aza-MBH) reaction of isatin-derived ketimines with MVK has been established by using chiral amino and phosphino catalysts, resulting in biomedically important 3-substituted 3-amino-2-oxindoles in good yields and with excellent enantioselectivity.
Abstract: The asymmetric catalytic aza-Morita–Baylis–Hillman (aza-MBH) reaction of isatin-derived ketimines with MVK has been established by using chiral amino and phosphino catalysts. The reaction resulted in biomedically important 3-substituted 3-amino-2-oxindoles in good yields (>80% for most cases) and with excellent enantioselectivity (90–99% ee). Twenty-eight cases assembled with chiral quaternary stereogenic centers have been examined under convenient systems.
TL;DR: A method which avoids metal and halogen for the synthesis of 3-arylthioindoles from indoles and diaryl disulfides using ammonium persulfate in methanol has been presented.
Abstract: A method which avoids metal and halogen for the synthesis of 3-arylthioindoles from indoles and diaryl disulfides using ammonium persulfate in methanol has been presented. Moreover, double C–H sulfenylation of indoles at 2 and 3-positions has also been achieved using iodine and ammonium persulfate.
TL;DR: The direct non-metallic trifluoromethylation of carbonyl compounds using fluoroform in the presence of t-Bu-P4 base afforded triffluorometHyl alcohols in high yields.
Abstract: A simple strategy avoiding the decomposition of a naked trifluoromethyl anion to difluorocarbene by a sterically very demanding organo-superbase without the help of a trifluoromethyl anion reservoir such as DMF is reported. The direct non-metallic trifluoromethylation of carbonyl compounds using fluoroform in the presence of t-Bu-P4 base afforded trifluoromethyl alcohols in high yields.
TL;DR: The utilization of a photo-induced synthon generated from N-phenyl glycine by an organic dye and visible light irradiation is disclosed and the intermediate could be coupled with either a radical or a nucleophile in a simple operation to afford several natural product-like compounds.
Abstract: The utilization of a photo-induced synthon generated from N-phenyl glycine by an organic dye and visible light irradiation is disclosed. The intermediate could be coupled with either a radical or a nucleophile in a simple operation to afford several natural product-like compounds.
TL;DR: A new NIR fluorescent probe, NIR-Pd, for palladium species was designed and synthesized, based on a HD NIR fluorophore and deprotection of aryl propargyl ethers by palladium, with high sensitivity and selectivity.
Abstract: A new NIR fluorescent probe, NIR-Pd, for palladium species was designed and synthesized, based on a HD NIR fluorophore and deprotection of aryl propargyl ethers by palladium. The probe NIR-Pd displayed either a large NIR fluorescence turn-on or ratiometric response to palladium with high sensitivity and selectivity. Additionally, the novel NIR probe can monitor palladium species in live HeLa cells by NIR fluorescence imaging.
TL;DR: A flow-based route to imatinib, the API of Gleevec, was developed and the general procedure was used to generate a number of analogues which were screened for biological activity against Abl1.
Abstract: A flow-based route to imatinib, the API of Gleevec, was developed and the general procedure then used to generate a number of analogues which were screened for biological activity against Abl1. The flow synthesis required minimal manual intervention and was achieved despite the poor solubility of many of the reaction components.
TL;DR: A tetrabutylammonium iodide catalyzed method for the synthesis of allyl aryl sulfone derivatives with Baylis-Hillman acetates and sulfonylhydrazides using tert-butyl hydroperoxide as an oxidation agent in water has been developed.
Abstract: A tetrabutylammonium iodide catalyzed method for the synthesis of allyl aryl sulfone derivatives with Baylis–Hillman acetates and sulfonylhydrazides using tert-butyl hydroperoxide as an oxidation agent in water has been developed. In this process, the group eliminated from the sulfonyl precursor is molecular nitrogen.
TL;DR: DNBSCy has the potential to measure the activity of glutathione reductase as a measure of oxidative stress as well as monitor the thiols in fetal bovine serum (FBS).
Abstract: We report a novel reaction-based thiol selective turn-on near-infrared (NIR) fluorescence and colourimetric dinitrobenzenesulfonyl-cyanine (DNBSCy) probe. In the presence of thiols such as glutathione (GSH), new absorption bands (476 and 581 nm) were observed, with the colour of the solution (10 mM PBS, pH = 7.4) changing from light green to blue. Interestingly, relatively non-fluorescent DNBSCy exhibited enhanced fluorescence emission around 700 nm in the NIR region. GSH reacted efficiently with the electron withdrawing sulfonyl ester moiety of DNBSCy, releasing the quinone embedded heptamethine cyanine (Cy-quinone) with extended π-electron conjugation responsible for the turn-on NIR fluorescence. Cy-quinone also displayed a conjugated π-electron push–pull character under physiological conditions. The DNBSCy probe was effectively employed to monitor the thiols in fetal bovine serum (FBS). The probe was capable of monitoring the oxidized glutathione (GSSG)/GSH redox process in the presence of glutathione reductase and NADPH with NIR fluorescence and colourimetric optical response. Thus, DNBSCy has the potential to measure the activity of glutathione reductase as a measure of oxidative stress.
TL;DR: Characterization of the rosemary ortholog CYP76AH4 led to the discovery that these CYPs simply hydroxylate the facilely oxidized aromatic intermediate abietatriene.
Abstract: Miltiradiene (1) is the precursor of phenolic diterpenoids such as ferruginol (2), requiring aromatization and hydroxylation. While this has been attributed to a single cytochrome P450 (CYP76AH1), characterization of the rosemary ortholog CYP76AH4 led to the discovery that these CYPs simply hydroxylate the facilely oxidized aromatic intermediate abietatriene (3).
TL;DR: GIAO NMR chemical shift calculations coupled with trained artificial neural networks (ANNs) have been shown to provide a powerful strategy for simple, rapid and reliable identification of structural misassignments of organic compounds using only one set of both computational and experimental data.
Abstract: GIAO NMR chemical shift calculations coupled with trained artificial neural networks (ANNs) have been shown to provide a powerful strategy for simple, rapid and reliable identification of structural misassignments of organic compounds using only one set of both computational and experimental data. The geometry optimization, usually the most time-consuming step in the overall procedure, was carried out using computationally inexpensive methods (MM+, AM1 or HF/3-21G) and the NMR shielding constants at the affordable mPW1PW91/6-31G(d) level of theory. As low quality NMR prediction is typically obtained with such protocols, the decision making was foreseen as a problem of pattern recognition. Thus, given a set of statistical parameters computed after correlation between experimental and calculated chemical shifts the classification was done using the knowledge derived from trained ANNs. The training process was carried out with a set of 200 molecules chosen to provide a wide array of chemical functionalities and molecular complexity, and the results were validated with a set of 26 natural products that had been incorrectly assigned along with their 26 revised structures. The high prediction effectiveness observed makes this method a suitable test for rapid identification of structural misassignments, preventing not only the publication of wrong structures but also avoiding the consequences of such a mistake.