Angewandte Chemie International Edition
Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Upcoming Hot Papers
Hot Papers are chosen by the Editors for their importance in a rapidly evolving field of high current interest. Many of the "Very Important Papers" (VIPs) would certainly qualify to be included here, but such a duplication is avoided.
Combining On-Chip Synthesis of a Focused Combinatorial Library with Computational Target Prediction Reveals Imidazopyridine GPCR Ligands
Michael Reutlinger, Tiago Rodrigues, Petra Schneider, Gisbert Schneider*
Creative combo: Microfluidic combinatorial synthesis was used along with computational target prediction to afford novel imidazopyridines with potent activity as adenosine A1/2B and adrenergic α1A/B receptor antagonists. The polypharmacology-driven design of molecular librarys and miniaturized flow synthesis hold great potential for drug discovery and chemical biology.
Published online, DOI: 10.1002/anie.201307786 – Read now
Graphene-Supported Ultrafine Metal Nanoparticles Encapsulated by Mesoporous Silica: Robust Catalysts for Oxidation and Reduction Reactions
Lu Shang, Tong Bian, Baihui Zhang, Donghui Zhang, Li-Zhu Wu, Chen-Ho Tung, Yadong Yin*, Tierui Zhang*
Layer cake: The synthesis of graphene-nanosheet-supported ultrafine metal nanoparticles encapsulated by thin mesoporous silica layers is reported. The resulting class of robust catalysts is shown to possess high activity, good stability under high temperature conditions, and excellent recyclability and reusability in both gas- and solution-phase reactions.
Published online, DOI: 10.1002/anie.201306863 – Read now
Observing High-Pressure Chemistry in Graphene Bubbles
Candy Haley Yi Xuan Lim, Milos Nesladek, Kian Ping Loh*
Graphene anvil: Graphene bubbles can be used as a bench-top anvil cell for studying high-pressure chemistry. Pressure-sensitive molecules that undergo conformational changes were used to probe the internal pressures inside the bubbles, which are 0.5–1 GPa over a temperature window of up to 673 K. The pressure-induced oligomerization of C60 molecules occurring at distinct P–T windows could be followed using FTIR spectroscopy.
Published online, DOI: 10.1002/anie.201308682 – Read now
An Effective Pd–Ni2P/C Anode Catalyst for Direct Formic Acid Fuel Cells
Jinfa Chang, Ligang Feng, Changpeng Liu, Wei Xing*, Xile Hu*
Giving Pd a boost: A novel Pd–Ni2P/C electrocatalyst has been developed for formic acid oxidation. A direct formic acid fuel cell integrating this catalyst showed superior power density and discharge stability than a state-of-the-art commercial Pd/C catalyst.
Published online, DOI: 10.1002/anie.201308620 – Read now
Therapeutic Targeting of Oncogenic K-Ras by a Covalent Catalytic Site Inhibitor
Sang Min Lim, Kenneth D. Westover, Scott B. Ficarro, Rane A. Harrison, Hwan Geun Choi, Michael E. Pacold, Martin Carrasco, John Hunter, Nam Doo Kim, Ting Xie, Taebo Sim, Pasi A. Jnne, Matthew Meyerson, Jarrod A. Marto, John R. Engen, Nathanael S. Gray*
Putting a stop to Ras: Two new selective, direct-acting covalent inhibitors of the K-Ras G12C mutant are reported. Studies suggest that the modification of K-Ras with SML-8-73-1 renders the protein inactive. These novel covalent inhibitors demonstrate that irreversible targeting of the K-Ras guanine-nucleotide binding site is potentially a viable therapeutic strategy for inhibition of Ras signaling.
Published online, DOI: 10.1002/anie.201307387 – Read now
Proteins with Highly Similar Native Folds Can Show Vastly Dissimilar Folding Behavior When Desolvated
Moritz Schennach, Kathrin Breuker*
Electron capture dissociation is used to study horse (example at the top) and tuna (example at the bottom) heart Cytochromes c in the complete absence of solvent. It is shown that in the absence of hydrophobic bonding, folding is slow, complex, and driven by electrostatic interactions. Y=Yield.
Published online, DOI: 10.1002/anie.201306838 – Read now
How Strain Affects the Reactivity of Surface Metal Oxide Catalysts
Kazuhiko Amakawa, Lili Sun, Chunsheng Guo, Michael Hävecker, Pierre Kube, Israel E. Wachs, Soe Lwin, Anatoly I. Frenkel, Anitha Patlolla, Klaus Hermann, Robert Schlögl, Annette Trunschke*
Only uncomfortable seats left: At high surface coverages of molybdenum oxide, at which surface hydroxy anchoring sites are limited, surface metal oxide molecules are forced to be anchored in strained/frustrated configurations. This strain leads to increased reactivity and explains the non-linear coverage dependence sometimes observed in monolayer-type supported metal oxide catalysts.
Published online, DOI: 10.1002/anie.201306620 – Read now
Palladium-Catalyzed Completely Linear-Selective Negishi Cross-Coupling of Allylzinc Halides with Aryl and Vinyl Electrophiles
Yang Yang, Thomas J. L. Mustard, Paul Ha-Yeon Cheong*, Stephen L. Buchwald*
Completely linear: The title reaction provides an effective means to access a wide range of prenylated arenes and "skipped dienes" in a completely linear-selective fashion, as demonstrated by a concise synthesis of the anti-HIV natural product siamenol. DFT calculations shed light on the origin of the excellent regioselectivity observed with the current Pd-based catalyst system.
Published online, DOI: 10.1002/anie.201308585 – Read now
Natural Products Discovery
Crowdsourcing Natural Products Discovery to Access Uncharted Dimensions of Fungal Metabolite Diversity
Lin Du, Andrew J. Robles, Jarrod B. King, Douglas R. Powell, Andrew N. Miller, Susan L. Mooberry*, Robert H. Cichewicz*
A fungus among us: A new Tolypocladium sp. was obtained through a crowdsourcing initiative. The expression of a silent biosynthetic pathway in this fungus was triggered through chemical epigenetics, culture medium manipulation, and co-culture to yield the unique polyketide-shikimate-NRPS-hybrid compound,
maximiscin, which demonstrated in vivo antitumor activity. NRPS=non-ribosomal peptide synthetase.
Published online, DOI: 10.1002/anie.201306549 – Read now
A Palladium-Nanoparticle and Silicon-Nanowire-Array Hybrid: A Platform for Catalytic Heterogeneous Reactions
Yoichi M. A. Yamada*, Yoshinari Yuyama, Takuma Sato, Shigenori Fujikawa, Yasuhiro Uozumi
An array of reactions: A silicon-nanowire-array-stabilized palladium-nanoparticle catalyst, SiNA-Pd is designed and used in the palladium-catalyzed Mizoroki–Heck reaction. It can catalyze a variety of other reactions and has a high reusability.
Published online, DOI: 10.1002/anie.201308541 – Read now
OLED Triplet Emitters
Metal-Free OLED Triplet Emitters by Side-Stepping Kasha´s Rule
Debangshu Chaudhuri, Eva Sigmund, Annemarie Meyer, Lisa Röck, Philippe Klemm, Sebastian Lautenschlager, Agnes Schmid, Shane R. Yost, Troy Van Voorhis, Sebastian Bange, Sigurd Höger*, John M. Lupton*
Keeping it light: Most organic fluorophores do not show useful emission from the triplet excited state. A new class of materials is presented for organic light-emitting diodes that exhibit phosphorescence under electrical excitation, even at room temperature, without employing the heavy-atom effect. Blocking of internal conversion is so effective that emission from higher-lying triplet states, above the singlet, can be observed at low temperature.
Published online, DOI: 10.1002/anie.201307601 – Read now No. 50/2013.
Bioinspired Total Synthesis of Montanine-Type Amaryllidaceae Alkaloids
Xu Bao, Ye-Xing Cao, Wen-Dao Chu, Hu Qu, Ji-Yuan Du, Xian-He Zhao, Xiao-Yan Ma, Cheng-Tao Wang, Chun-An Fan*
Finding a common path: A synthetic strategy inspired by the proposed biogenesis of the montanine-type alkaloids enabled the concise asymmetric synthesis of these compounds in a divergent fashion on the basis of an unprecedented tandem oxidative dearomatization/intramolecular aza-Michael addition as the key step. This bioinspired approach revealed a chemical connection between the cherylline- and montanine-type alkaloids (see scheme).
Published online, DOI: 10.1002/anie.201307324 – Read now
The Catalytic Asymmetric α-Benzylation of Aldehydes
Benjamin List*, Ilija Čorić, Oleksandr O. Grygorenko, Philip S. J. Kaib, Igor Komarov, Anna Lee, Markus Leutzsch, Subhas Chandra Pan, Andrey V. Tymtsunik, Manuel van Gemmeren
A sterically demanding proline derivative promotes the first aminocatalyzed α-alkylation of α-branched aldehydes with benzyl bromides as alkylating agents. Racemic α-branched aldehydes react with alkylating agents in a DYKAT process to give the corresponding α-alkylated aldehydes with quaternary stereogenic centers in good yields and high enantioselectivities.
Published online, DOI: 10.1002/anie.201306037 – Read now
Natural Gas to Fuels and Chemicals: Improved Methane Aromatization in an Oxygen-Permeable Membrane Reactor
Zhengwen Cao, Heqing Jiang*, Huixia Luo, Stefan Baumann, Wilhelm A. Meulenberg, Jens Assmann, Leslaw Mleczko, Yi Liu, Jürgen Caro*
Adding value with membranes: Improved methane aromatization was achieved by using an oxygen-permeable membrane. The resulting membrane reactor shows a superior methane conversion and a higher resistance towards catalyst deactivation.
Published online, DOI: 10.1002/anie.201307935 – Read now
Structure-Based Design of an RNA-Binding p-Terphenylene Scaffold that Inhibits HIV-1 Rev Protein Function
Luis González-Bulnes, Ignacio Ibáñez, Luis M. Bedoya, Manuela Beltrán, Silvia Catalán, José Alcamí*, Santos Fustero*, José Gallego*
Rev(ersing) RNA binding: RNA-binding inhibitors based on a bilaterally substituted p-terphenylene scaffold (green) project their substituents in a broad spatial angle and reproduce the interactions of a protein α-helix (red) embedded in its RNA receptor. These terphenyls can mimic one α-helix of the HIV-1 protein Rev and inhibit Rev function and HIV-1 replication in cells. This scaffold may open new avenues for targeting nucleic acids with small molecules.
Published online, DOI: 10.1002/anie.201306665 – Read now No. 50/2013.
Ultrasensitive and Fast Bottom-up Analysis of Femtogram Amounts of Complex Proteome Digests
Liangliang Sun, Guijie Zhu, Yimeng Zhao, Xiaojing Yan, Si Mou, Norman J. Dovichi*
Femtogram proteomics: An ultrasensitive capillary zone electrophoresis–mass spectrometry system that is based on an improved nanospray interface has been developed. This system is used for the analysis of picogram to femtogram amounts of E. coli digests; for example, over 100 proteins were identified from 16 pg digests by tandem mass spectrometry. AMTs=accurate mass and time tags.
Published online, DOI: 10.1002/anie.201308139 – Read now
Preparation of Small-Molecule Microarrays by trans-Cyclooctene Tetrazine Ligation and Their Application in the High-Throughput Screening of Protein–Protein Interaction Inhibitors of Bromodomains
Chong-Jing Zhang, Chelsea Y. J. Tan, Jingyan Ge, Zhenkun Na, Grace Y. J. Chen, Mahesh Uttamchandani, Hongyan Sun, Shao Q. Yao*
Fast and efficient: A library of trans-cyclooctene (TCO)-modified small molecules were immobilized on tetrazine-functionalized glass slides by using the fastest bioorthogonal reaction known. The resulting small-molecule microarray was screened against a variety of human bromodomains to identify protein–protein interaction inhibitors.
Published online, DOI: 10.1002/anie.201307803 – Read now
Regulating Angiogenesis with Light-Inducible AntimiRs
Florian Schäfer, Jasmin Wagner, Andrea Knau, Stefanie Dimmeler*, Alexander Heckel*
The inhibition of microRNAs (miRs) in a spatiotemporally defined manner by an exogenous trigger would help to specifically target the biological activity and avoid off-target effects. Novel antimiRs directed against miR-92a can be activated by irradiation (see scheme; 3'-UTR=3'-untranslated region) In this way miR-92a is inhibited, the miR-92a target integrin α5 is derepressed, and angiogenesis of endothelial cells is enhanced.
Published online, DOI: 10.1002/anie.201307502 – Read now
Scalable Synthesis of Oxazolones from Propargylic Alcohols through Multistep Palladium(II) Catalysis: β-Selective Oxidative Heck Coupling of Cyclic Sulfonyl Enamides and Aryl Boroxines
Santosh Kumar Alamsetti, Andreas K. Å. Persson, Tuo Jiang, Jan-E. Bäckvall*
A whale of a scale: The title oxidative Heck coupling proceeded with unusual β selectivity to generate a variety of branched substituted oxazolones (see scheme; Ts=p-toluenesulfonyl). The three-step synthesis from readily available starting materials with a simple palladium catalyst and inexpensive reagents could be carried out in a single reaction vessel or scaled up for the preparation of large amounts of these amino acid precursors.
Published online, DOI: 10.1002/anie.201307471 – Read now
Biological Imaging Using Nanoparticles of Small Organic Molecules with Fluorescence Emission at Wavelengths Longer than 1000 nm
Zhimin Tao, Guosong Hong, Chihiro Shinji, Changxin Chen, Shuo Diao, Alexander L. Antaris, Bo Zhang, Yingping Zou, Hongjie Dai*
Embedded in a polymer: A hydrophobic organic molecule that fluoresces in the near-infrared II (NIR-II) region was made water-soluble and biocompatible by its embedment in a polymer nanoparticle, which was then coated with hydrophilic polyethylene glycol chains. The resulting nanoparticles exhibit bright fluorescence in the NIR-II window and high photostability in aqueous media and were used for in vivo imaging in mice.
Published online, DOI: 10.1002/anie.201307346 – Read now No. 49/2013.
Micromotor-Based High-Yielding Fast Oxidative Detoxification of Chemical Threats
Jahir Orozco, Guanzhi Cheng, Diana Vilela, Sirilak Sattayasamitsathit, Rafael Vazquez-Duhalt, Gabriela Valdés-Ramírez, On Shun Pak, Alberto Escarpa, Chengyou Kan, Joseph Wang*
Oxidative decontamination: An effective strategy for the oxidative neutralization of organophosphorus nerve agents that is based on self-propelled micromotors has been developed. The movement of multiple motors across a peroxide-activated contaminated solution enhances the decontamination efficiency compared with common neutralization processes for chemical warfare agents.
Published online, DOI: 10.1002/anie.201308072 – Read now No. 50/2013.
Magnetically Triggered Dual Functional Nanoparticles for Resistance-Free Apoptotic Hyperthermia
Dongwon Yoo, Heeyeong Jeong, Seung-Hyun Noh, Jae-Hyun Lee, Jinwoo Cheon*
Overcoming resistance: Heat-treated cancer cells possess a protective mechanism for resistance and survival. Resistance-free apoptosis-inducing magnetic nanoparticles (RAINs) successfully promote hyperthermic apoptosis, obstructing cell survival by triggering two functional units of heat generation and the release of geldanamycin (GM) for heat shock protein (Hsp) inhibition under an alternating magnetic field (AMF).
Published online, DOI: 10.1002/anie.201306557 – Read now No. 49/2013.
Plant Biosynthetic Pathways
Minimum Set of Cytochromes P450 for Reconstituting the Biosynthesis of Camalexin, a Major Arabidopsis Antibiotic
Andrew P. Klein, Gülbenk Anarat-Cappillino, Elizabeth S. Sattely*
Bringing it all together: The missing key step in the biosynthesis of camalexin was uncovered by in vitro biochemical characterization. The coupling of Trp- and Cys-derived fragments through C–S bond formation (see scheme, right) is promoted by an unusual cytochrome P450 CYP71A13. The in vitro reconstitution of the camalexin biosynthesis (left) from Trp and Cys was achieved using just three cytochromes P450. IAN=indole-3-acetonitrile.
Published online, DOI: 10.1002/anie.201307454 – Read now
Catalytic Enantioselective Synthesis of Functionalized Tropanes Reveals Novel Inhibitors of Hedgehog Signaling
Rishikesh Narayan, Jonathan O. Bauer, Carsten Strohmann, Andrey P. Antonchick*, Herbert Waldmann*
Dipolar cycloaddition: A highly efficient copper(I)-catalyzed enantioselective [3+2] cycloaddition reaction of 1,3-fused cyclic azomethine ylides and nitroalkenes has been developed. This method provides access to functionalized tropane scaffolds with several quaternary and tertiary stereocenters in a single step under mild reaction conditions.
Published online, DOI: 10.1002/anie.201307392 – Read now No. 49/2013.
Visible-Light Photocatalytic Conversion of Carbon Monoxide to Methane by Nickel(II) Oxide
Francesc Sastre, Avelino Corma*, Hermenegildo García*
Solar Fuels: Different n- and p-type semiconductor have been investigated for sustainable solar fuel production. p-Type semiconductors such as NiO, Fe3O4, Co3O4, and CuO are able to reduce carbon monoxide by water or hydrogen to methane (see picture). The highest CH4 yield achieved was 17.26 mmol of CH4 per gram of catalyst using NiO in an excess of H2.
Published online, DOI: 10.1002/anie.201307851 – Read now No. 49/2013.
One-Pot Zinc-Promoted Asymmetric Alkynylation/Brook-Type Rearrangement/Ene–Allene Cyclization: Highly Selective Formation of Three New Bonds and Two Stereocenters in Acyclic Systems
Polina Smirnov, Jomon Mathew, Anne Nijs, Einat Katan, Miriam Karni, Carsten Bolm, Yitzhak Apeloig, Ilan Marek*
ItÂ´s as easy as 1, 2, 3: In a one-pot sequence, two stereocenters and three new bonds were created with high selectivity through an asymmetric alkynylation of acyl silanes, a tandem Brook-type rearrangement and Zn–ene–allene cyclization, the addition of an electrophile, and finally oxidation (see scheme). The straightforward nature of the synthetic procedure contrasts strongly with the complexity of the densely functionalized products obtained.
Published online, DOI: 10.1002/anie.201306749 – Read now
Electrochemical Sizing of Organic Nanoparticles
Wei Cheng, Xiao-Fei Zhou, Richard G. Compton*
The size of organic nanoparticles (NPs) can be electrochemically determined by Faradaic charge transfer when nanoparticles strike an electrode. Indigo NPs were used as a model (see distribution of the NP diameter). This strategy could be used for monitoring the size of a wide range of organic nanoparticles.
Published online, DOI: 10.1002/anie.201307653 – Read now No. 49/2013.
Thiophosphoramide-Based Cooperative Catalysts for Brønsted Acid Promoted Ionic Diels–Alder Reactions
Alina Borovika, Pui-In Tang, Seth Klapman, Pavel Nagorny*
Threes a crowd: The combination of a Brønsted acid and a hydrogen-bond donor cocatalyst was found to promote various ionic [2+4] cycloadditions under mild reaction conditions (see scheme; Ts=4-toluenesulfonyl). Thiophosphoramides are the most effective cocatalysts because of the stronger counterion activation effect resulting from three, rather than two, hydrogen bonds involved in anion binding.
Published online, DOI: 10.1002/anie.201307133 – Read now No. 50/2013.
Selective Exo-Enzymatic Labeling of N-Glycans on the Surface of Living Cells by Recombinant ST6Gal I
Ngalle Eric Mbua, Xiuru Li, Heather R. Flanagan-Steet, Lu Meng, Kazuhiro Aoki, Kelley W. Moremen, Margreet A. Wolfert, Richard Steet*, Geert-Jan Boons*
A game of tag: N-Glycans on the surface of living cells were selectively tagged by exogenously administering recombinant ST6Gal I sialyltransferase and azide-modified CMP-Neu5Ac. This modification was followed by a strain-promoted cycloaddition using a biotin-modified dibenzylcyclooctynol (red star=biotin). The methodology will make it possible to dissect the mechanisms that underlie altered glycoconjugate recycling and storage in disease.
Published online, DOI: 10.1002/anie.201307095 – Read now No. 49/2013.
Thiols and Selenols as Electron-Relay Catalysts for Disulfide-Bond Reduction
John C. Lukesh III, Brett VanVeller, Ronald T. Raines*
Pass them on! Dithiobutylamine immobilized on a resin is a useful reagent for the reduction of disulfide bonds. Its ability to reduce a disulfide bond in a protein is enhanced greatly if used along with a soluble strained cyclic disulfide or mixed diselenide that relays electrons from the resin to the protein. This electron-relay catalysis system provides distinct advantages over the use of excess soluble reducing agent alone.
Published online, DOI: 10.1002/anie.201307481 – Read now No. 49/2013.
Optical Chemical Sensor
A Noble-Metal-Free Porous Coordination Framework with Exceptional Sensing Efficiency for Oxygen
Rui-Biao Lin, Fang Li, Si-Yang Liu, Xiao-Lin Qi, Jie-Peng Zhang*, Xiao-Ming Chen
Light material: By virtue of the unique framework structure and very high oxygen permeability, a noble-metal-free, highly fluorescent, porous coordination polymer demonstrates a rapid, reversible, efficient, stable, and selective fluorescence-quenching response toward oxygen.
Published online, DOI: 10.1002/anie.201307217 – Read now No. 50/2013.
Highly Enantioselective Bromocyclization of Tryptamines and Its Application in the Synthesis of (−)-Chimonanthine
Weiqing Xie*, Guangde Jiang, Huan Liu, Jiadong Hu, Xixian Pan, Hui Zhang, Xiaolong Wan, Yisheng Lai*, Dawei Ma*
A shorter path: A highly enantioselective bromocyclization of tryptamine has been developed using an anionic chiral phase-transfer catalyst. This method provides a direct approach for preparing chiral
3-bromopyrroloindoline from tryptamine, which enables a four-step enantioselective synthesis of (−)-chimonanthine. PG=protecting group.
Published online, DOI: 10.1002/anie.201306774 – Read now No. 49/2013.
A Directional Entropic Force Approach to Assemble Anisotropic Nanoparticles into Superlattices
Kaylie L. Young, Michelle L. Personick, Michael Engel, Pablo F. Damasceno, Stacey N. Barnaby, Reiner Bleher, Tao Li, Sharon C. Glotzer*, Byeongdu Lee*, Chad A. Mirkin*
Not touching but sticking: By using cationic surfactant micelles as depletants, a directional entropic force approach (DEFA) assembles anisotropic nanoparticles into superlattices in solution. The micelles induce the face-to-face stacking of the nanoparticles to maximize the systemÂ´s entropy. The shape of the nanoparticles determines the symmetry of the superlattice, the interparticle spacing is determined by the charged surfactant.
Published online, DOI: 10.1002/anie.201306009 – Read now
Diastereoselective Synthesis of Eight-Membered-Ring Allenes from Propargylic Epoxides and Aldehydes by Silylene Insertion into Carbon–Oxygen Bonds
Christina Z. Rotsides, Chunhua Hu, K. A. Woerpel*
Bent out of shape: Silver-catalyzed insertions of silylenes into propargylic C–O bonds of epoxides regioselectively form 1,2-silaoxetanes, which add to aldehydes to give the title allenes as single diastereomers (see scheme; Ts=4-toluenesulfonyl). An X-ray crystal structure confirmed the stereochemistry of the allene, which is bent significantly from linearity (164°).
Published online, DOI: 10.1002/anie.201306093 – Read now No. 49/2013.