Showing papers in "Organic and Biomolecular Chemistry in 2012"

Strategies for the enantioselective synthesis of spirooxindoles.

Abstract: Oxindoles and spirooxindoles are important synthetic targets that are often considered to be prevalidated with respect to their biological activity and applications for pharmaceutical lead discovery This review features efficient strategies for the enantioselective synthesis of spirocyclic oxindoles, focusing on reports in 2010 and 2011 Although enantioselective synthesis remains an ongoing challenge, exciting recent advances in this area feature spirooxindoles with greater complexity, up to eight stereogenic centers, more practical synthetic methods, and new catalytic activation strategies Developments in catalyst systems and reaction conditions have shown that many reactions can be optimized to control selectivity and provide access to isomeric products, which are important for biological testing This review is organized based on two primary disconnection strategies, and then further subdivided into the type and ring size of the spirocycle that is generated Strategies are also compared for the synthesis of non-spirocyclic 3,3′-disubstituted oxindoles

A one-pot catalysis: the strategic classification with some recent examples

Abstract: In this “Emerging Area”, the strategic classification of one-pot catalysis, i.e. cooperative, relay and sequential catalysis, is described. In order to illustrate this classification, we take the readers through a series of recent examples which utilize either metal-metal, metal-organo and organo-organo catalysts. The compilation clearly demonstrates the explosive growth and power of this field, which has become, in the last few years, an important technique particularly in the case of enantioselective catalysis.

Small molecule control of bacterial biofilms

Abstract: Bacterial biofilms are defined as a surface attached community of bacteria embedded in a matrix of extracellular polymeric substances that they have produced. When in the biofilm state, bacteria are more resistant to antibiotics and the host immune response than are their planktonic counterparts. Biofilms are increasingly recognized as being significant in human disease, accounting for 80% of bacterial infections in the body and diseases associated with bacterial biofilms include: lung infections of cystic fibrosis patients, colitis, urethritis, conjunctivitis, otitis, endocarditis and periodontitis. Additionally, biofilm infections of indwelling medical devices are of particular concern, as once the device is colonized infection is virtually impossible to eradicate. Given the prominence of biofilms in infectious diseases, there has been an increased effort toward the development of small molecules that will modulate bacterial biofilm development and maintenance. In this review, we highlight the development of small molecules that inhibit and/or disperse bacterial biofilms through non-microbicidal mechanisms. The review discuses the numerous approaches that have been applied to the discovery of lead small molecules that mediate biofilm development. These approaches are grouped into: (1) the identification and development of small molecules that target one of the bacterial signaling pathways involved in biofilm regulation, (2) chemical library screening for compounds with anti-biofilm activity, and (3) the identification of natural products that possess anti-biofilm activity, and the chemical manipulation of these natural products to obtain analogues with increased activity.

“Frustrated Lewis pair” hydrogenations

Abstract: This perspective article discusses developments of metal-free hydrogenation catalysts derived from “frustrated Lewis pair” (FLP) systems. The range of catalysts uncovered and the applications to reductions of imines, aziridines, enamines, silyl enol ethers, diimines, metallocene derivatives and nitrogen-based heterocycles are described. In addition, FLP aromatic reduction of aniline derivatives to the cyclohexylamine analogs is discussed. The potential applications of these metal-free reductions are considered.

Combined experimental and theoretical studies on the photophysical properties of cycloparaphenylenes

Abstract: We studied the UV-vis absorption and fluorescence in solution/solid states of [n]cycloparaphenylene ([n]CPP: n = 9, 12, 14, 15, and 16), and conducted theoretical studies to better understand the experimental results. The representative experimental findings include (i) the most intense absorption maxima (λabs1) display remarkably close values (338–339 nm), (ii) the longest-wavelength absorption maxima (λabs2) are blue-shifted with increasing the ring size (395 → 365 nm), (iii) the emission maxima (λem) are blue-shifted with increasing the ring size (494 → 438 nm for longest-wavelength maxima), (iv) the fluorescent quantum yields (ΦF) in solution are high (0.73–0.90), (v) the fluorescence lifetimes (τs) of [9]- and [12]CPP are 10.6 and 2.2 ns, respectively, and (vi) the ΦF values slightly increase in polymer matrix but significantly decrease in the crystalline state. According to TD-DFT calculations, the longest-wavelength absorption (λabs2) corresponds to a forbidden HOMO → LUMO transition and the most intense absorption (λabs1) corresponds to degenerate HOMO − 1 → LUMO and HOMO → LUMO + 1 transitions with high oscillator strength. The interesting and counterintuitive optical properties of CPPs (constant λabs1 and blue shift of λabs2) could be ascribed mainly to the ring-size effect in frontier molecular orbitals (in particular the increase of the HOMO–LUMO gap as the number of benzene rings increases). On the basis of comparative calculations using hypothetical model geometries, we conclude that the unique behavior of HOMO and LUMO of CPPs is due mainly to their lack of a conjugation length dependence in combination with a significant bending effect (particularly to HOMO) and a torsion effect (particularly to LUMO).

Imidazole derivatives: a comprehensive survey of their recognition properties.

Abstract: Due to its amphoteric nature the imidazole ring can function as selective and effective anion and/or cation and even neutral organic molecules receptor system. As a result, the design of new multichannel imidazole-based receptors capable of recognizing different types of analytes is strongly demanded. This review summarizes the most recent and relevant advances in this area.

Degree of molecular self-sorting in multicomponent systems

Abstract: Self-sorting represents the spontaneous and high fidelity self and/or non-self-recognition of two or more related components within a complex mixture. While the effective management of self-sorting principles perceptibly requires some key expertise in molecular programming, at a higher stage of operation it is of supreme interest to guide the process to increasingly higher degrees of self-sorting. In this article, we present the emerging principles of how to guide several components toward formation of self-sorted multicomponent architectures. To provide further guidance in denominating such systems, we suggest to utilise a systematic classification as well as a formula to evaluate their degree of self-sorting (M).

Recent advances and applications of iridium-catalysed asymmetric allylic substitution

Abstract: Since their discovery in 1997, iridium-catalysed asymmetric allylic substitutions have been developed into a broadly applicable tool for the synthesis of chiral building blocks via C–C and C–heteroatom bond formation. The remarkable generality of these reactions and the high levels of regio- and enantioselectivity that are usually obtained in favour of the branched products have been made possible by a thorough investigation of the catalyst system and its mode of action. Therefore, today the Ir-catalysed asymmetric allylic substitution is a powerful reaction in the organic chemist's repertoire and has been used extensively for several applications. This article aims to provide an overview of the development of iridium catalysts derived from an Ir salt and a chiral phosphoramidite and their application to the enantioselective synthesis of natural products and biologically relevant compounds.

Squaraine dyes in PDT: from basic design to in vivo demonstration

Abstract: The design and development of novel squaraine dyes as sensitisers for photodynamic therapy (PDT) applications has grown tremendously in the last decade from the time when a squaraine dye was proposed to be a potential candidate, to-date when the use of such dyes have been demonstrated in animal models for skin cancer. This perspective article highlights the basic design, tuning of absorption, triplet excited state and two-photon absorption properties and recent developments of the squaraines as PDT sensitisers.

Solvent and substituent effects on aggregation constants of perylene bisimide π-stacks – a linear free energy relationship analysis

Abstract: A series of six perylene bisimides (PBIs) with hydrophilic and hydrophobic side chains at the imide nitrogens were applied for a comparative study of the solvent and structural effects on the aggregation behaviour of this class of dyes. A comparison of the binding constants in tetrachloromethane at room temperature revealed the highest binding constant of about 105 M−1 for a PBI bearing 3,4,5-tridodecyloxyphenyl substituents at the imide nitrogens, followed by 3,4,5-tridodecylphenyl and alkyl-substituted PBIs, whereas no aggregation could be observed in the accessible concentration range for PBIs equipped with bulky 2,6-diisopropylphenyl substituents at the imide nitrogens. The aggregation behaviour of three properly soluble compounds was investigated in 17 different solvents covering a broad polarity range from nonpolar n-hexane to highly polar DMSO and water. Linear free energy relationships (LFER) revealed a biphasic behaviour between Gibbs free energies of aggregation and common empirical solvent polarity scales indicating particularly strong π–π stacking interactions in nonpolar aliphatic and polar alcoholic solvents whilst the weakest binding is observed in dichloromethane and chloroform. Accordingly, PBI aggregation is dominated by electrostatic interactions in nonpolar solvents and by solvophobic interactions in protic solvents. In water, the aggregation constant is increased far beyond LFER expectations pointing at a pronounced hydrophobic effect.

Tunnelling control of chemical reactions--the organic chemist's perspective.

Abstract: Even though quantum mechanical tunnelling has been appearing recurrently mostly in theoretical studies that emphasize its decisive role for many chemical reactions, it still appears suspicious to most organic chemists. Recent experiments in combination with powerful computational approaches, however, have demonstrated that tunnelling must be included to fully understand chemical reactivity. Here we provide an overview of the importance of tunnelling in organic chemical reactions.

A selective colorimetric and ratiometric fluorescent probe for hydrogen sulfide

Abstract: A reaction-based colorimetric and ratiometric fluorescent probe based on an ICT-strategy for selective detection of H2S that exploited the H2S-mediated reduction of nitrocompound to amines was explored. And it displayed high selectivity for H2S over other relevant reactive sulfur, oxygen, nitrogen species and other anions with more than 120 nm blue shift and the change of emission intensity ratio inducted by H2S was over 4750.

Simple copper/TEMPO catalyzed aerobic dehydrogenation of benzylic amines and anilines

Abstract: CuBr2 with 2,2,6,6-tetramethylpiperidyl-1-oxy (TEMPO) has been successfully employed for the aerobic oxidation of primary and secondary benzyl amines in aqueous acetonitrile. Such catalytic systems have previously been used extensively in alcohol oxidation reactions. The same catalyst system was also used for oxidative cross-couplings of benzylamines with anilines. The electronic and steric properties of the aniline partner were found to be of crucial importance in determining reactivity or lack thereof. A mechanism for these reactions is proposed based on the data obtained to date. In the absence of benzyl amines, electron-rich anilines were found to undergo dehydrogenative coupling and yields of the resulting azo products could be increased by replacing CuBr2 with CuBr. No ligand (e.g.pyridine) is required for either reaction to proceed and presumably water and acetonitrile solvate the copper-containing intermediates.

A seminaphthofluorescein-based fluorescent chemodosimeter for the highly selective detection of cysteine

Abstract: A fluorescent chemodosimeter for cysteine detection was developed based on a tandem conjugate addition and intramolecular cyclization reaction. The method exhibited an excellent selectivity for cysteine over other biothiols such as homocysteine and glutathione.

Ruthenium-catalysed oxidative synthesis of heterocycles from alcohols

Abstract: Ruthenium-catalysed hydrogen transfer has been successfully used for the conversion of alcohols into either 2,3-dihydroquinazolines or quinazolines. The choice of reaction conditions allows for the selective formation of either heterocycle and the methodology can also be applied to the sulfonamide analogue.

Diastereoselective synthesis of vicinal amino alcohols

Abstract: The vicinal amino alcohol is a common motif in natural products and pharmaceuticals. Amino acids constitute a natural, inexpensive, and enantiopure choice of starting material for the synthesis of such functionalities. However, the matters concerning diastereoselectivity are not obvious. This Perspective takes a look in the field of diastereoselective synthesis of vicinal amino alcohols starting from amino acids using various methods.

Modulation of the antioxidant activity of phenols by non-covalent interactions

Abstract: Non-covalent (H-bonding) interactions, either intramolecular or with the surrounding medium, have a major influence on the activity of natural and synthetic phenolic antioxidants, due to the modulation of their reactivity with radical species, such as peroxyl radicals. Different cases can be distinguished. (i) Intra- or inter-molecular H-bonding involving the reactive –OH moiety will depress the antioxidant activity if the –OH acts as H-bond donor, while the opposite will generally occur if it acts as H-bond acceptor. (ii) Remote intra- and inter-molecular H-bonding, involving a distant –OH group (in polyphenols) or a ring substituent, may increase or decrease the reactivity of an antioxidant toward free radicals, depending on whether the stabilization produced by the H-bond increases or decreases along the reaction coordinate, on proceeding from reactants to the transition state. In this Perspective, the role of non-covalent interactions in the complex chemistry of natural polyphenolic antioxidants is discussed with the aid of literature data on simplified model compounds, aiming at the composition of a clear picture that might guide future research.

Rhodium-catalyzed regioselective amidation of indoles with sulfonyl azides via C-H bond activation.

Abstract: Direct C-2 amidation of indoles was reported using sulfonyl azides as the amino source to release N2 as the single byproduct. This reaction exhibits high functional group tolerance and regioselectivity, providing a variety of 2-amino substituted indoles in high to excellent yield. The procedure is robust, reliable, and compatible with water and air.

Complexation of neutral 1,4-dihalobutanes with simple pillar[5]arenes that is dominated by dispersion forces.

Abstract: The complexation of neutral 1,4-dihalobutanes with simple pillar[5]arenes was investigated. The results indicate the formation of interpenetrated complexes, where the dispersive interactions dominate the complex stability. Typically, 1,4-diiodobutane displays the strongest binding strength with ethylpillar[5]arene [Ka = (1.0 ± 0.1) × 104 M−1], up to 120 fold as compared with 1,4-difluorobutane.

Discovery, application and protein engineering of Baeyer–Villiger monooxygenases for organic synthesis

Abstract: Baeyer–Villiger monooxygenases (BVMOs) are useful enzymes for organic synthesis as they enable the direct and highly regio- and stereoselective oxidation of ketones to esters or lactones simply with molecular oxygen. This contribution covers novel concepts such as searching in protein sequence databases using distinct motifs to discover new Baeyer–Villiger monooxygenases as well as high-throughput assays to facilitate protein engineering in order to improve BVMOs with respect to substrate range, enantioselectivity, thermostability and other properties. Recent examples for the application of BVMOs in synthetic organic synthesis illustrate the broad potential of these biocatalysts. Furthermore, methods to facilitate the more efficient use of BVMOs in organic synthesis by applying e.g. improved cofactor regeneration, substrate feed and in situ product removal or immobilization are covered in this perspective.

Pyridostatin analogues promote telomere dysfunction and long-term growth inhibition in human cancer cells

Abstract: The synthesis, biophysical and biological evaluation of a series of G-quadruplex interacting small molecules based on a N,N′-bis(quinolinyl)pyridine-2,6-dicarboxamide scaffold is described. The synthetic analogues were evaluated for their ability to stabilize telomeric G-quadruplex DNA, some of which showed very high stabilization potential associated with high selectivity over double-stranded DNA. The compounds exhibited growth arrest of cancer cells with detectable selectivity over normal cells. Long-time growth arrest was accompanied by senescence, where telomeric dysfunction is a predominant mechanism together with the accumulation of restricted DNA damage sites in the genome. Our data emphasize the potential of a senescence-mediated anticancer therapy through the use of G-quadruplex targeting small molecules based on the molecular framework of pyridostatin.

Thiol-yne coupling: revisiting old concepts as a breakthrough for up-to-date applications.

Abstract: Radical thiol–yne coupling (TYC) has emerged as one of the most appealing click chemistry procedures, appearing as a sound candidate for replacing/complementing other popular click reactions such as the thiol–ene coupling (TEC) and the Cu-catalysed azide–alkyne cycloaddition (CuAAC). Radical TYC is indeed a metal-free reaction suitable for biomedical applications, and its mechanistic features often make it more efficient than its TEC sister reaction and more suitable for multifaceted derivatisations in the materials chemistry and bioconjugation realms. This article reviews the fascinating results obtained in those fields in very recent years.

Highly selective colorimetric sensing of cyanide based on formation of dipyrrin adducts

Abstract: Cyanide sensing has attracted increasing interest due to its toxicity and wide use in industrial activities. Herein, we developed three colorimetric cyanide sensors by the modification of the α-position of a dipyrrin chromophore with various carbonyl groups, namely, C6F5CO, C6H5CO and CHO for 1, 2 and 3, respectively. In dichloromethane, these sensors respond to both CN− and F− with distinct colour changes. UV-Vis, 1H NMR and HRMS measurements imply a two-process interaction between the sensors and CN−. Initially, CN− forms a hydrogen bond with the NH moiety, and then it attacks the carbonyl group of the sensors via a nucleophilic addition reaction. In contrast, in aqueous systems, only cyanide induced vivid solution colour changes from light yellow to pink via nucleophilic addition reactions. The CN− detection limits reach a micromolar level of 3.6 × 10−6 M, 4.2 × 10−6 M and 7.1 × 10−6 M for 1, 2 and 3, respectively. In view of the easy synthesis and the highly selective recognition of CN− with vivid colour changes, 1–3 may be developed as a novel and promising prototype of selective and sensitive colorimetric cyanide sensors.

Recent progress of core-substituted naphthalenediimides: highlights from 2010

Abstract: Core-substituted naphthalenediimides (cNDIs) are rapidly emerging as a powerful strategy to create functional nanomaterials and their implications in biological and supramolecular chemistry are significant. Recent developments in the synthesis of cNDIs have allowed several groups to probe the function of this interesting class of dye molecules in a molecular and supramolecular sense. Core-substitution of the NDI can be seen as an opportunity to extend the planar, rigid core and could be used to prepare novel structures for applications in organic, biosupramolecular chemistry, biomedicine, materials science and organic solar cells. In this Emerging Area, we provide up-to-date recent progress in the field of cNDIs. We begin with a general discussion and the applications of cNDIs in the field of supramolecular chemistry i.e. generation of nanostructures such as vesicles and nanotubes etc., and we also discuss advances in artificial photosynthesis. Following this is a section on their implications in the field of sensors, particularly DNA intercalation, anion sensing and NDI based pH sensors. Finally, we explore the recent development of cNDIs in organic solar cell applications. We conclude with our views on the prospects of cNDIs in future research.

Chiral quaternary phosphonium salts: a new class of organocatalysts

Abstract: Phase-transfer catalysis has widely been used as a prime synthetic tool for both laboratory and industrial processes. During the last twenty years, asymmetric phase-transfer catalysis using chiral organocatalysts has attracted widespread interest. However, the scope of chiral phase-transfer catalysis has been limited mostly to the quaternary ammonium salts. As an emerging area, the recent developments in the application of quaternary phosphonium salts as chiral phase-transfer catalysts are discussed in this article.

Palladium-catalyzed desulfitative arylation of azoles with arylsulfonyl hydrazides

Abstract: Palladium-catalyzed desulfitative and denitrogenative arylation of azoles with arylsulfonyl hydrazides has been achieved. A broad scope of azoles and arylsulfonyl hydrazides has been used to produce arylated azoles in high yields.

One-pot synthesis of 1,2,3-triazoles from boronic acids in water using Cu(II)–β-cyclodextrin complex as a nanocatalyst

Abstract: We report here the one-pot synthesis of 1,2,3-triazoles of arylboronic acids in water. An efficient method has been developed for the synthesis of 1,2,3-triazoles via a one-pot reaction of an arylboronic acid with sodium azide in the presence of Cu2–β-CD (CD = Cyclodextrin) as a nanocatalyst in water followed by a click cyclization reaction with an alkyne at room temperature in air without any additives. This method is simple, rapid, and high yielding.

2-Iodo-imidazolium receptor binds oxoanions via charge-assisted halogen bonding.

Abstract: A detailed 1H-NMR study of the anion binding properties of the 2-iodo-imidazolium receptor 1 in DMSO allows to fully attribute the observed affinities to strong charge-assisted C–I⋯X−halogen bonding (XB). Stronger binding was observed for oxoanions over halides. Phosphate, in particular, binds to 1 with an association constant of ca. 103 M−1, which is particularly high for a single X-bond. A remarkably short C–I⋯O− contact is observed in the structure of the salt 1·H2PO4−.

A prototype continuous-flow liquid–liquid extraction system using open-source technology

Abstract: A prototype continuous-flow liquid–liquid extraction system is reported. By harnessing several open-source software libraries, a computer control script was written using the Python programming language. Using a ‘computer-vision’ approach, this allowed the computer to monitor the interface level between the organic and aqueous phases using a simple webcam setup and (by dynamically controlling pump flow rate) to keep this interface within defined limits. The system enabled the efficient ‘inline’ extraction of excess reagent in hydrazone formations, dithiane formations and epoxidations. The initial results of dispersion measurement are also presented.

Palladium-catalysed aminosulfonylation of aryl-, alkenyl- and heteroaryl halides: scope of the three-component synthesis of N-aminosulfonamides.

Abstract: By using DABCO·(SO2)2, DABSO, as a solid bench-stable SO2-equivalent, the palladium-catalysed aminosulfonylation of aryl-, alkenyl- and heteroaryl halides has been achieved. N,N-Dialkylhydrazines are employed as the N-nucleophiles and provide N-aminosulfonamides as the products in good to excellent yields. The reactions are operationally simple to perform, requiring only a slight excess of SO2 (1.2–2.2 equiv.), and tolerate a variety of substituents on the halide coupling partner. Variation of the hydrazine component is also demonstrated. The use of N,N-dibenzylhydrazine as the N-nucleophile delivers N-aminosulfonamide products that can be converted into the corresponding primary sulfonamides using a high-yielding, telescoped, deprotection sequence. The ability to employ hydrazine·SO2 complexes as both the N-nucleophile and SO2 source is also illustrated.