Fast α-oxyamination of stable enolates, silyl enol ethers, and in situ deprotonated dialkyl 2-oxoalkane phosphonates and diphenyl-2-oxoalkyl phosphine oxides was performed in the presence of [Ru(bpy)₃]²⁺ (bpy = 2,2′-bipyridyl) as a photocatalyst, 2,2,6,6-tetramethylpiperidine nitroxide (TEMPO), and visible light. The key step was the light-induced one-electron oxidation of TEMPO into the 2,2,6,6-tetramethylpiperidine-1-oxoammonium ion, which was nucleophilically attacked to yield α-functionalized carbonyl compounds. The reaction time was significantly reduced by the use of the microreactor flow technique.

Extracts of Ruscus aculeatus L., known as butcher's broom, are mainly used for the treatment of chronic venous insufficiency (CVI). In a recent study on the phenolic compounds of Rusci rhizoma, new phenyl-1-benzoxepinols were isolated. As the therapeutic effect of butcher's broom is ascribed to the pharmacological activity of the main constituents, steroidal saponins and their aglycones the ruscogenins, the role of the newly identified compounds was of interest. Owing to the low availability of the compounds by isolation, we synthesized them for pharmacological testing. In an ORAC–fluorescein assay they revealed a significant antioxidative activity, which may contribute to the anti-inflammatory properties of the phenolic fraction obtained from Rusci rhizoma extracts.

Degradation of the materials in organic light-emitting devices (OLEDs) is the major impediment for the development of economically feasible, highly efficient and durable devices for commercial applications. Even though this chemical degradation is complex and the least understood of the different degradation modes in OLEDs, scientists were successful in providing insight into some of the responsible processes. In this progress report we will review recent advances in the elucidation of chemical degradation mechanisms: First possible reasons for defect formation and the most common and important methods to investigate those processes are covered before discussing the reactions and their products for the different types of materials present in a device. We summarize commonalities in the occurring mechanisms, and identify structural features and moieties that can be detrimental to operational stability. Some of the resulting implications on the development of new materials are presented and backed by concrete examples from literature.

Deoxygenation is an extensively studied field in organic chemistry, and over the last decades many methods such as the Barton–McCombie deoxygenation reaction or deoxygenation with alkali metals in liquid ammonia have been established. Within this microreview, we discuss different strategies for the chemoselective catalytic deoxygenation of alcohols with special attention to their scope and limitations. The deoxygenation of derivatives of alcohols and their direct deoxygenation as step-economic alternative are covered with current examples. Catalytic methods can serve as convenient and economic alternatives for established methods in the reduction of carbon–oxygen single bonds.

Diazoniumsalze werden bereits seit 1896 zur Erzeugung von Arylradikalen und zur Arylierung von C-H-Bindungen eingesetzt. Aufbauend auf Arbeiten von Pschorr entwickelte Meerwein in der Mitte des letzten Jahrhunderts eine allgemeine Methode zur Arylierung von Olefinen. Jedoch konnte die Reaktion nicht neben den neueren übergangsmetallkatalysierten C(sp²)-C(sp²)-Kupplungen bestehen. Der Einsatz von Photoredoxkatalyse zur Einelektronenübertragung bietet nun eine bessere Möglichkeit der Aktivierung von Aryldiazoniumsalzen. Nachdem die erste photokatalytische Pschorr-Reaktion bereits 1984 beschrieben worden war, folgte im letzten Jahr eine Reihe von Publikationen über Anwendungen der photokatalytischen Meerwein-Arylierung in Aryl-Alken-Kreuzkupplungen. Dieser Kurzaufsatz fasst die Ursprünge und die Anwendungsbreite der Reaktion zusammen und stellt neueste Entwicklungen vor.

The use of diazonium salts for aryl radical generation and CH arylation processes has been known since 1896 when Pschorr first used the reaction for intramolecular cyclizations. Meerwein developed it further in the early 1900s into a general arylation method. However, this reaction could not compete with the transition-metal-mediated formation of C(sp²)C(sp²) bonds. The replacement of the copper catalyst with iron and titanium compounds improved the situation, but the use of photocatalysis to induce the one-electron reduction and activation of the diazonium salts is even more advantageous. The first photocatalyzed Pschorr cyclization was published in 1984, and just last year a series of papers described applications of photocatalytic Meerwein arylations leading to aryl–alkene coupling products. In this Minireview we summarize the origins of this reaction and its scope and applications.

Biological membranes play a key role for the function of living organisms. Thus, many artificial systems have been designed to mimic natural cell membranes and their functions. A useful concept for the preparation of functional membranes is the embedding of synthetic amphiphiles into vesicular bilayers. The dynamic nature of such noncovalent assemblies allows the rapid and simple development of bio-inspired responsive nanomaterials, which find applications in molecular recognition, sensing or catalysis. However, the complexity that can be achieved in artificial functionalized membranes is still rather limited and the control of their dynamic properties and the analysis of membrane structures down to the molecular level remain challenging.

This work reports the combinatorial synthesis and screening of phosphorescent iridium complexes as solution processable emitters for OLEDs. The approach taken here allows for the rapid synthesis, isolation, spectroscopic characterization and identification of the libraries based on chromatographic methods. Subsequent analysis of the irradiation induced degradation provides insight on the stability of the complexes under continuous excitation. The method is versatile and can easily be applied to other metal complexes or organic dyes for various applications, e.g., in electroluminescence, photovoltaics and sensing.

An efficient and general synthesis of hexahydropyrimidopyrimidinediones has been developed employing a low melting L-(+)-tartaric acid-dimethylurea mixture as reaction medium. The melt acts at the same time as solvent, catalyst and reactant. Functionalized hexahydropyrimidopyrimidinediones are obtained in good to excellent yields after simple work-up.

We describe novel scaffold designs for nonpeptidic α-helix mimetics. The tricyclic scaffolds contain triazoles and reproduce amino acid side chains i, i+3, and i+7. The three different scaffolds are synthetically readily accessible, allow the introduction of further substituents to increase the versatility, and are suitable for library design. A modular synthesis route using Cu^I- and Ru^II-catalyzed azide–alkyne [3+2] cycloadditions as central steps was developed. To demonstrate the methodology, we have prepared a library of compounds containing all three scaffolds.

A series of water-soluble bis- and tetrakis-Zn^II–cyclen complexes with rigid structures was prepared to enhance the carboxylate and phosphate ion binding response in contrast to analogues with less-confined molecular structures. Boc-protected 6-chloro-1,3,5-triazine–bis-cyclen was coupled to different aryl and alkyl moieties in moderate to high yields and subsequently converted into the corresponding bis- or tetrakis-Zn^II–cyclen complexes. The bis-Zn^II–cyclen moiety is known for its affinity to anions. Depending on the arene substituent some of the synthesized synthetic receptors are luminescent. They were studied by absorption and emission spectroscopy for their response to the presence of phosphate anions of biological relevance in buffered aqueous solution at neutral pH and for their affinity to the genetically encodable oligoaspartate and glutamate sequences (D₄ and E₄ tag) recently introduced. The rigid structures of the compounds enhance the electronic coupling between the metal complex binding site and the reporter dye. This leads to an increased anion binding response in homogeneous aqueous solution.

Hybrid compounds combining a luminescent aza crown ether and 1,4,7,10-tetraazacyclododecane (cyclene) or bis(pyridin-2-ylmethylamine) (bpa) metal complexes were prepared. These synthetic receptors signal the presence of peptidic ammonium phosphates in buffered aqueous solution by changes in their emission intensity. Reversible phosphate ion coordination to the metal complex binding sites decreases the emission intensity of the phthalic ester fluorophore. Structurally suitable ammonium phosphates, such as the C-terminal domain of RNA polymerase II or the protein kinase G target sequence, bind to the synthetic receptors by an additional intramolecular interaction between the ammonium ion and the aza crown ether. The binding of the ammonium ion to the aza crown ether increases the emission intensity of the fluorophore. In aqueous solution, this weak interaction can only occur within aggregates of phosphates and metal complex receptors of matching geometry;therefore, it allows the distinction of structurally related phosphorylated peptides in buffered aqueous solution.

The modulation of biological signal transduction pathways by masking phosphorylated amino acid residues represents a viable route toward pharmacologic protein regulation. Binding of phosphorylated amino acid residues has been achieved with synthetic metal-chelate receptors. The affinity and selectivity of such receptors can be enhanced if combined with a second binding site. We demonstrate this principle with a series of synthetic ditopic metal-chelate receptors, which were synthesized and investigated for their binding affinity to phosphorylated short peptides under conditions of physiological pH. The compounds showing highest affinity were subsequently used to inhibit the interaction of the human STAT1 protein to a peptide derived from the interferon-γ receptor, and between the checkpoint kinase Chk2 and its preferred binding motif. Two of the investigated ditopic synthetic receptors show a significant increase in inhibition activity. The results show that regulation of protein function by binding to phosphorylated amino acids is possible. The introduction of additional binding sites into the synthetic receptors increases their affinity, but the flexibility of the structures investigated so far prohibited stringent amino acid sequence selectivity in peptide binding. Copyright © 2009 John Wiley & Sons, Ltd.

Benzyl alcohols are oxidized cleanly and efficiently to the corresponding aldehydes under irradiation using flavin photocatalysts and aerial oxygen as the terminal oxidant in homogeneous aqueous solution. Turnover frequencies (TOF) of more than 800 h⁻¹ and turnover numbers (TON) of up to 68 were obtained. Several flavin photocatalysts with fluorinated or hydrophobic aliphatic chains were immobilized on solid supports like fluorous silica gel, reversed phase silica gel or entrapped in polyethylene pellets. The catalytic efficiency of the heterogeneous photocatalysts was studied for the oxidation of different benzyl alcohols in water and compared to the analogous homogeneous reactions. Removal of the heterogeneous photocatalyst stops the reaction conversion immediately, which shows that the immobilized flavin is the catalytically active species. The immobilized catalysts are stable, retain their reactivity if compared to the corresponding homogeneous systems and are easily removed from the reaction mixture and reused. TOF of up to 26 h⁻¹, TON of 280 and up to 3 reaction cycles without loss of activity are possible with the heterogeneous flavin photocatalysts.

Proteins are vital for basically every known organism. Therefore the investigation of their structure, the development of a deeper understanding of protein–protein interactions and the design of novel peptides, which selectively interact with proteins are fields of active research. Small peptides consisting of the 20 natural amino acids typically show high conformational flexibility and a low in-vivo stability which hampers their application as tools in medicinal diagnostics or molecular biology. One very versatile strategy to overcome such drawbacks is the use of peptidomimetics. These are small molecules which mimic natural peptides or proteins and thus produce the same biological effects as their natural role models. As the field of peptidomimetics is developing fast this review can only provide selected approaches together with examples and is not intended to be comprehensive. We focus on the discussion of amino acid modifications, backbone modifications, global restrictions by cyclisation and on synthetic backbone scaffolds. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

New tetracyclic analogues of forskolin have been prepared by derivatization of the natural product. Treatment of a forskolin-derived cyclic thionocarbonate with 1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine resulted in the formation of a seven-membered cyclic carbonate derivative by an unprecedented rearrangement of an intermediate dialkoxycarbene or 1,3-dipole, whereas radical deoxygenation was followed by intramolecular cyclization with the double bond to form a third analogue. Two of the new analogues were investigated for their ability to activate adenylyl cyclases 1, 2 and 5. The introduction of another ring into the forskolin skeleton did not lead to a loss of binding affinity to the enzyme. Although the new compounds are much more spacious than forskolin, they still seem to fit into the binding pocket and were found to be partial agonists.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Self-assembled vesicular polydiacetylene (PDA) particles with embedded metal complex receptor sites have been prepared. The particles respond to the presence of ATP and PPi (pyrophosphate) in buffered aqueous solution by visible changes of their color and emission properties. Blue PDA vesicles of uniform size of about 200 nm were obtained upon UV irradiation from mono- and dinuclear zinc(II)–cyclen and iminodiacetato copper [Cu^II–IDA] modified diacetylenes, embedded in amphiphilic diacetylene monomers. Addition of ATP and PPi to the PDA vesicle solution induces a color change from blue to red observable by the naked eye. The binding of ATP and PPi changes the emission intensity. Other anions such as ADP, AMP, H₂PO₄⁻, CH₃COO⁻, F⁻, Cl⁻, Br⁻ and I⁻, failed to induce any spectral changes. The zinc(II)–cyclen nanoparticles are useful for the facile detection of PPi and ATP in millimolar concentrations in neutral aqueous solutions, while Cu^II–IDA modified vesicular PDA receptors are able to selectively discriminate between ATP and PPi.

This microreview summarizes recent reports on the preparation of metal complex peptide conjugates by solid-phase synthesis methods. Procedures for such conjugates are in many cases different from standard solid-phase peptide synthesis protocols. Specific advantages of general strategies, the synthesis of peptide–ligand conjugates and complexation with excess metal ions on solid support or the incorporation of previously prepared metal complex amino acid derivatives are discussed.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Although vast information about the coordination ability of amino acids and peptides to metal ions is available, little use of this has been made in the rational design of selective peptide receptors. We have combined a copper(II) nitrilotriacetato (NTA) complex with an ammonium-ion-sensitive and luminescent benzocrown ether. This compound revealed micromolar affinities and selectivities for glycine- and histidine-containing sequences, which closely resembles those of copper(II) ion peptide binding: the two free coordination sites of the copper(II) NTA complex bind to imidazole and amido nitrogen atoms, replicating the initial coordination steps of non-complexed copper(II) ions. The benzocrown ether recognizes the N-terminal amino moiety intramolecularly, and the significantly increased emission intensity signals the binding event, because only if prior coordination of the peptide has taken place is the intramolecular ammonium ion–benzocrown ether interaction of sufficient strength in water to trigger an emission signal. Intermolecular ammonium ion–benzocrown ether binding is not observed. Isothermal titration calorimetry confirmed the binding constants derived from emission titrations. Thus, as deduced from peptide coordination studies, the combination of a truncated copper(II) coordination sphere and a luminescent benzocrown ether allows for the more rational design of sequence-selective peptide receptors.

Despite its popularity and widespread use, the efficacy of Echinacea products remains unclear and controversial. Among the various compounds isolated from Echinacea, ketoalkenes and ketoalkenynes exclusively found in the pale purple coneflower (E. pallida) are major components of the extracts. In contrast to E. purpurea alkamides, these compounds have not been synthesized and studied for immunostimulatory effects. We present a practical and useful synthetic approach to the ketoalkenes using palladium-catalyzed cross-coupling reactions and the pharmaceutical results at the human cannabinoid receptors. The synthetic route developed provides overall good yields for the ketoalkenes and is applicable to other natural products with similar 1,4-diene motifs. No significant activity was observed at either receptor, indicating that the ketoalkenes from E. pallida are not responsible for immunomodulatory effects mediated via the cannabinergic system. However, newly synthesized non-natural analogues showed micro-molar potency at both cannabinoid receptors.

Irradiation of a palladium catalyst bearing UV-A-absorbing phosphine ligands with low-intensity UV-A light leads to higher conversions of reactants at lower temperatures and an increased selectivity towards the cross-coupling product in Suzuki–Miyaura- and Stille-type reactions. The examples studied illustrate that a selective energy input into the catalyst by irradiation leads to more selective conversions under milder reaction conditions. With the availability of affordable and energy-efficient UV-A LED light sources, selective heating of the catalyst by light can be envisaged as a general strategy to increase the performance of a catalyst.

Artificial ditopic receptors for the differentiation of phosphorylated peptides varying in i+3 amino acid side chains were synthesized, and their binding affinities and selectivities were determined. The synthetic receptors show the highest binding affinities to phosphorylated peptides under physiological conditions (HEPES, pH 7.5, 154 mM NaCl) reported thus far for artificial systems. The tight and selective binding was achieved by high cooperativity of the two binding moieties in the receptor molecules. All receptors interact with phosphorylated serine by bis(Zn^II–cyclen) complex coordination and a second binding site recognizing a carboxylate or imidazole amino acid side chain functionality.

Upon irradiation, flavin oxidises 4-methoxybenzyl alcohol to the corresponding aldehyde using aerial O₂ as the terminal oxidant. We have observed that this reaction is significantly accelerated by the presence of thiourea. A series of thiourea-functionalised flavins has been prepared from flavin isothiocyanates and their photocatalytic efficiencies have been monitored by NMR. The alcohol photooxidation proceeds rapidly and cleanly with high turnover numbers of up to 580, exceeding previously reported performances. A likely mechanistic rationale for the more than 30-fold acceleration of the photo–redox reaction by thiourea has been derived from spectroscopic, electrochemical, and kinetic studies. Thus, thiourea acts as an electron-transfer mediator for the initial photooxidation of 4-methoxybenzyl alcohol by the excited flavins. This mechanism has similarities to electron-relay mechanisms in flavoenzymes, for which cysteine sulfenic acid intermediates are proposed. The observation that thiourea mediates flavin photo–redox processes is valuable for the design of more sophisticated photocatalysts based on Nature's best redox chromophore.