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The title compound, [FePt(C 19 H 18 OS 2 )(C 18 H 15 P)(C 25 H 22 P 2 )(CO) 2 ], 1 , [(OC) 2 Fe(μ-dppm)(μ-C(=O)C(CH 2 SC 6 H 4 Me-4)=CCH 2 SC 6 H 4 Me-4)Pt(PPh 3 )], represents the first example of a diphosphane-bridged heterobimetallic Fe-Pt dimetalla-cyclo-pentenone complex resulting from a bimetallic activation of metal-coordinated carbonyl ligand with an inter-nal alkyne, namely 1,4-bis-( p -tolyl-thio)-but-2-yne. The bridging μ 2 -C(=O)C(CH 2 SC 6 H 4 Me-4)=CCH 2 SC 6 H 4 Me-4 unit (stemming from a carbon-carbon coupling reaction between CO and the triple bond of the alkyne di-thio-ether) forms a five-membered dimetalla-cyclo-pentenone ring, in which the C=C bond is π-coordinated to the Fe center. The latter is connected to the Pt center through a short metal-metal bond of 2.5697 (6) Å., (© Mohamed et al. 2020.)

The complete mol-ecule of the hexa-metallic title complex, namely, tetra-bromido-tetra-μ-hydroxido-hexa-kis-[μ-2-methyl-3-(pyrrolidin-1-yl)propan-2-olato]hexa-zinc(II) acetone disolvate, [Zn 6 Br 4 (C 9 H 18 NO) 4 (OH) 4 ]·2C 3 H 6 O 2 , is generated by a crystallographic centre of symmetry. Two of the unique zinc atoms adopt distorted ZnO 2 NBr tetra-hedral coordination geometries and the other adopts a ZnO 3 N tetra-hedral arrangement. Both unique alkoxide ligands are N , O -chelating and both hydroxide ions are μ 2 bridging. The crystal structure displays an O-H⋯O hydrogen bond between a μ 2 -OH group and an acetone solvent mol-ecule. The Hirshfeld surface has been calculated and is described., (© Scheel et al. 2020.)

The title compounds, hexa-kis-[μ 3 -2-(di-methyl-amino)-ethano-lato]hexa-μ 2 -iso-propano-lato-μ 4 -oxido-tetra-deca-lithium(I), [Li 7 ( i -PrO) 3 (C 4 H 10 NO) 3 ] 2 O ( 1 ), and {3-[(2-meth-oxy-eth-yl)(meth-yl)amino]-1,1-dimethylpropano-lato}diiso-prop-an-o-lsodium(I), [Na( i -PrOH) 2 (C 8 H 18 NO 2 )] ( 2 ), were crystallized in the presence of 2-propanol ( i -PrOH, C 3 H 7 OH). The structure 1 has monoclinic symmetry ( C 2/ c ) and the asymmetric unit contains half of the compound. Title compound 2 has triclinic symmetry ( P ) and the asymmetric unit is half of an inversion-symmetric aggregate. Both compounds consist of an alkali metal, an amino-alkoxide and a 2-propanol compound. Furthermore, the dimeric sodium aggregate 2 is build up by hydrogen bonding through the 2-propanol and the alkoxides. Compound 1 does not exhibit hydrogen bonding, due to the fact that the 2-propanol is deprotonated. In compound 1 , benzene appeared as co-crystallate, but was suppressed by solvent masking because of strong disorder. The formula mass and density do not take account of the solvent., (© Scheel et al. 2020.)

A novel one-pot [3+2]-cycloaddition reaction of (E)- 3-arylidene-1-phenyl-succinimides, cyclic 1,2-diketones (isatin, 5-chloro-isatin and acenaphtenequinone), and diverse α- aminoacids such as 2-phenylglycine or sarcosine is reported. The reaction provides succinimide-substituted dispiropyrrolidine derivatives with high regio- and diastereoselectivities under mild reaction conditions. The stereochemistry of these N- heterocycles has been confirmed by four X-ray diffraction studies. Several synthetized compounds show higher inhibition on acetylcholinesterase (AChE) than butyrylcholinesterase (BChE). Of the 17 synthesized compounds tested, five exhibit good AChE inhibition with IC 50 of 11.42 to 22.21 µM. A molecular docking study has also been undertaken for compound 4n possessing the most potent AChE inhibitory activity, disclosing its binding to the peripheral anionic site of AChE enzymes.

With the objective to establish a correlation between the spacer distance and halide dependence on the structural features of coordination polymers (CPs) assembled by the reaction between CuX salts (X = Cl, Br, I) and dithioether ligands BzS(CH 2 ) n SBz ( n = 1-9; Bz = benzyl), a series of 26 compounds have been prepared and structurally investigated. A particular attention has been devoted to the design of networks with extremely long and flexible methylene spacer units between the SBz donor sites. Under identical conditions, CuI and CuBr react with BzSCH 2 Bz ( L1 ) affording respectively the one-dimensional (1D) CPs {Cu(μ 2 -I) 2 Cu}(μ- L1 ) 2 ] n ( CP1 ) and {Cu(μ 2 -Br) 2 Cu}(μ- L1 ) 2 ] ( CP2 ), which incorporate Cu(μ 2 -X) 2 Cu rhomboids as secondary building units (SBUs). The hitherto unknown architecture of two-dimensional (2D) layers obtained with CuCl ( CP3 ) differs from that of CP1 and CP2 , which bear inorganic -Cl-Cu-Cl-Cu-Cl- chains interconnected through bridging L1 ligands, thus forming a 2D architecture. The crystallographic characterization of a 1D CP obtained by reacting CuI with 1,3-bis(benzylthio)propane ( L2 ) reveals that [{Cu(μ 2 -I) 2 Cu}(μ- L2 ) 2 ] n ( CP4 ) contains conventional Cu 2 I 2 rhomboids as SBUs. In contrast, unusual isostructural CPs [{Cu(μ 2 -X)}(μ 2 - L2 )] n ( CP5 ) and ( CP6 ) are obtained with CuX when X = Br and Cl, respectively, in which the isolated Cu atoms are bridged by a single μ 2 -Br or μ 2 -Cl ion giving rise to infinite [Cu(μ 2 -X)Cu] n ribbons. The crystal structure of the strongly luminescent three-dimensional (3D) polymer [{Cu 4 (μ 3 -I) 3 (μ 4 -I)(μ- L3 ) 1.5 ] n ( CP7 ) issued from reacting 2 equiv of CuI with BzS(CH 2 ) 4 SBz ( L3 ) has been redetermined. CP7 features unusual [(Cu 4 I 3 )(μ 4 -I)] n arrays securing the 3D connectivity. In contrast, mixing CuI with an excess of L3 provides the nonemissive material [{Cu(μ 2 -I) 2 Cu}(μ- L3 ) 2 ] n ( CP8 ). Treatment of CuBr and CuCl with L3 leads to [{Cu(μ 2 -Br) 2 Cu}(μ- L3 ) 2 ] n ( CP9 ) and the 0D complex [{Cu(μ 2 -Cl) 2 Cu}(μ- L3 ) 2 ] ( D1 ), respectively. The crystallographic particularity for CP9 is the coexistence of two topological isomers within the unit cell. The first one, CP9 - 1D , consists of simple 1D ribbons running along the a axis of the unit cell. The second topological isomer, CP9 - 2D , also consists of [Cu(μ 2 -Br) 2 Cu] SBUs, but these are interconnected in a 2D manner forming 2D sheets placed perpendicular to the 1D ribbons. Four 2D CPs, namely, [{Cu 4 (μ 3 -I) 4 }(μ- L4 ) 2 ] n ( CP10 ), [{Cu(μ 2 -I) 2 Cu}(μ- L4 ) 2 ] n ( CP11 ), [{Cu(μ 2 -Br) 2 Cu}(μ- L4 ) 2 ] n ( CP12 ), and [{Cu(μ 2 -Cl) 2 Cu}(μ- L4 ) 2 ] n ( CP13 ), stem from the self-assembly process of CuX with BzS(CH 2 ) 6 SBz ( L4 ). A similar series of 2D materials comprising [{Cu 4 (μ 3 -I) 4 }(μ- L5 ) 2 ] n ( CP14 ), [{Cu(μ 2 -I) 2 Cu}(μ- L5 ) 2 ] n ( CP15 ), [{Cu(μ 2 -Br) 2 Cu}(μ- L5 ) 2 ] n ( CP16 ), and [{Cu(μ 2 -Cl) 2 Cu}(μ- L5 ) 2 ] n ( CP17 ) result from the coordination of BzS(CH 2 ) 7 SBz ( L5 ) on CuX. Ligation of CuX with the long-chain ligand BzS(CH 2 ) 8 SBz ( L6 ) allows for the X-ray characterization of the luminescent 2D [{Cu 4 (μ 3 -I) 4 }(μ- L6 ) 2 ] n ( CP18 ) and the isostructural 1D series [{Cu(μ 2 -X) 2 Cu}(μ- L6 ) 2 ] n CP19 ( X = I), CP20 (X = Br) and CP21 (X = Cl). Noteworthy, BzS(CH 2 ) 9 SBz ( L7 ) bearing a very flexible nine-atom chain generated the crystalline materials 2D [{Cu 4 (μ 3 -I) 4 }(μ- L7 ) 2 ] n ( CP22 ) and the isostructural 1D series [{Cu(μ 2 -X) 2 Cu}(μ- L6 ) 2 ] n CP23 (X = I), CP24 (X = Br), and CP25 (X = Cl), featuring nanometric separations between the cubane- or rhomboid-SBUs. This comparative study reveals that the outcome of the reaction of CuX with the shorter ligands BzS(CH 2 ) n SBz ( n = 1-4) is not predictable. However, with more flexible spacer chains BzS(CH 2 ) n SBz ( n = 6-9), a clear structural pattern can be established. Using a 1:1 CuX-to-ligand ratio, [{Cu(μ 2 -X) 2 Cu}(μ- L4-7 ) 2 ] CPs are always formed, irrespectively of L4 - L7 . Employing a 2:1 CuX-to-ligand ratio, only CuI is able to form networks incorporating Cu 4 (μ 3 -I) 4 clusters as SBUs. All attempts to construct polynuclear cluster using CuBr and CuCl failed. The materials have been furthermore analyzed by powder X-ray diffraction, Raman spectroscopy, and thermogravimetric analysis, and the photophysical properties of the emissive materials have been studied.

The title compound, C 22 H 22 O 2 S 2 , 1 , represents an example of an ortho -vanillin-based functionalized di-thio-ether, which could be useful as a potential chelating ligand or bridging ligand for coordination chemistry. This di-thio-acetal 1 crystallizes in the ortho-rhom-bic space group Pbca . The phenyl rings of the benzyl groups and that of the vanillin unit form dihedral angles of 35.38 (6) and 79.77 (6)°, respectively. The crystal structure, recorded at 100 K, displays both weak intra-molecular O-H⋯O and inter-molecular O-H⋯S hydrogen bonding., (© Raghuvanshi et al. 2020.)

The crystal structure of the title compound, C 10 H 13 N·3H 2 O, a heterocyclic amine, was determined in the presence of water. The compound co-crystallizes with three water mol-ecules in the asymmetric unit, which leads to the formation of hydrogen bonding in the crystal., (© Langenohl et al. 2020.)

The presence of metal centers with often highly conserved coordination environments is crucial for roughly half of all proteins, having structural, regulatory, or enzymatic function. To understand and mimic the function of metallo-enzymes, bioinorganic chemists pursue the challenge of synthesizing model compounds with well-defined, often heteroleptic metal sites. Recently, we reported the design of tailored homoleptic coordination environments for various transition metal cations based on unimolecular DNA G-quadruplex structures, templating the regioselective positioning of imidazole ligandosides L I . Here, we expand this modular system to more complex, heteroleptic coordination environments by combining L I with a new benzoate ligandoside L B within the same oligonucleotide. The modifications still allow the correct folding of parallel tetramolecular and antiparallel unimolecular G-quadruplexes. Interestingly, the incorporation of L B results in strong destabilization expressed in lower thermal denaturation temperatures T m . While no transition metal cations could be bound by G-quadruplexes containing only L B , heteroleptic derivatives containing both L = +34°C. The here shown system represents an important step toward the design of more complex coordination environments inside DNA scaffolds, promising to culminate in the preparation of functional metallo-DNAzymes. I and L B were found to complex Cu II , Ni II , and Zn II . Especially in case of Cu II we found strong stabilizations of up to Δ T m = +34°C. The here shown system represents an important step toward the design of more complex coordination environments inside DNA scaffolds, promising to culminate in the preparation of functional metallo-DNAzymes., (Copyright © 2020 Punt, Stratmann, Sevim, Knauer, Strohmann and Clever.)

The polymeric title compound, [Cu 2 (C 2 H 3 N) 2 (C 3 H 6 S 2 ) 2 ](PF 6 ) 2 , represents an example of a one-dimensional coordination polymer resulting from the reaction of [Cu(MeCN) 4 ][PF 6 ] with 1,3-di-thiol-ane. The cationic one-dimensional ribbon consists of two copper(I) centers each ligated by one aceto-nitrile mol-ecule and inter-connected through two bridging 1,3-di-thiol-ane ligands. One S-donor site of each ligand is κ 1 -bound to Cu, whereas the second S atom acts as a four-electron donor, bridging two Cu atoms in a κ 4 -bonding mode. The positive charge of each copper cation is compensated for by a hexa-fluorido-phosphate counter-ion. In the crystal, the polymer chains are linked by a series of C-H⋯F hydrogen bonds, forming a supra-molecular framework., (© Knauer et al. 2020.)

A "branching-folding" synthetic strategy that affords a range of diverse cyclic benzo-sulfonamide scaffolds is presented. Whereas different annulation reactions on common ketimine substrates build the branching phase of the scaffold synthesis, a common hydrogenative ring-expansion method, facilitated by an increase of the ring-strain during the branching phase, led to sulfonamides bearing medium-sized rings in a folding pathway. Cell painting assay was successfully employed to identify tubulin targeting sulfonamides as novel mitotic inhibitors., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

The title compound, [FePt(C 12 H 12 O)(C 18 H 15 P)(C 25 H 22 P 2 )(CO) 2 ]·2C 7 H 8 ·CH 2 Cl 2 or [(OC) 2 Fe(μ-dppm)(μ-C(=O)C(2,4,5-C 6 H 2 Me 3 )=CH)Pt(PPh 3 )], represents an example of a diphosphane-bridged heterobimetallic dimetalla-cyclo-pentenone complex resulting from a bimetallic activation of 1-ethynyl-2,4,5-tri-methyl-benzene and a metal-coordinated carbonyl ligand. The bridging μ 2 -C(=O)C(2,4,5 - C 6 H 2 Me 3 )=CH unit (stemming from a carbon-carbon coupling reaction between CO and the terminal alkyne) forms a five-membered dimetalla-cyclo-pentenone ring, in which the C=C bond is π-coordinated to the Fe centre. The latter is connected to the Pt centre through a short metal-metal bond of 2.5770 (5) Å. In the crystal, the complex is solvated by one di-chloro-methane and two toluene mol-ecules., (© Brieger et al. 2019.)

Precision medicine has revolutionized the treatment of patients in EGFR driven non-small cell lung cancer (NSCLC). Targeted drugs show high response rates in genetically defined subsets of cancer patients and markedly increase their progression-free survival as compared to conventional chemotherapy. However, recurrent acquired drug resistance limits the success of targeted drugs in long-term treatment and requires the constant development of novel efficient inhibitors of drug resistant cancer subtypes. Herein, we present covalent inhibitors of the drug resistant gatekeeper mutant EGFR-L858R/T790M based on the pyrrolopyrimidine scaffold. Biochemical and cellular characterization, as well as kinase selectivity profiling and western blot analysis, substantiate our approach. Moreover, the developed compounds possess high activity against multi drug resistant EGFR-L858R/T790M/C797S in biochemical assays due to their highly reversible binding character, that was revealed by characterization of the binding kinetics. In addition, we present the first X-ray crystal structures of covalent inhibitors in complex with C797S-mutated EGFR which provide detailed insight into their binding mode., (This journal is © The Royal Society of Chemistry 2019.)

Cancer cells sustain growth by altering their metabolism to accelerated aerobic glycolysis accompanied by increased glucose demand and employ glutamine as additional nutrient source. This metabolic adaptation induces upregulation of glucose transporters GLUT-1 and -3, and simultaneous targeting of both transporters and of glutamine metabolism may offer a promising approach to inhibit cancer cell growth. We describe the discovery of the very potent glucose uptake inhibitor Glutor, which targets glucose transporters GLUT-1, -2, and -3, attenuates glycolytic flux and potently and selectively suppresses growth of a variety of cancer cell lines. Co-treatment of colon cancer cells with Glutor and glutaminase inhibitor CB-839 very potently and synergistically inhibits cancer cell growth. Such a dual inhibition promises to be particularly effective because it targets the metabolic plasticity as well as metabolic rescue mechanisms in cancer cells., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Weighting both the basicity and nucleophilicity of an organolithium compound is crucial for an effective use of these reagents in syntheses. To achieve this, an aggregate of optimal size and reactivity has to be formed by adding suitable donating agents. Against usual expectations, this is not inevitably the smallest possible aggregate. In this work, we show that the monomeric complex of (trimethylsilyl)methyllithium stabilized by the bidentate ligand (R,R)-TMCDA shows no significant reactivity. In contrast, two dimeric aggregates stabilized by monodentate quinuclidine were obtained, exhibiting enhanced reactivity compared to the parent compound and to the monomeric complex.

We present a mechanistic proposal for the desymmetrisation of dimethoxy silanes with alkyllithiums. The stereochemical pathway is highly defined by the coordination of the metal lithium, which suppresses the reversible interconversion of the various pentavalent intermediates. The predicted kinetic control of the stereoinduction is verified by the experiments using a planar chiral ferrocene backbone.

The parent compound 1,3-dithiane (L1) was reacted with CuI providing the 1D coordination polymer [{Cu(μ 2 -I) 2 Cu}(μ 2 -L1) 2 ] n (CP1), an isostructural compound [{Cu(μ 2 -Br) 2 Cu}(μ 2 -L1) 2 ] n (CP2) was isolated upon treatment of CuBr with L1. In contrast, treatment of L1 with CuCl results in the formation of 2D polymeric [{Cu(μ 2 -Cl) 2 Cu}(μ 2 -L1)] n (CP3), in which each sulfur atom acts as a 4-electron donor. The 1D compounds [{Cu(μ 2 -X) 2 Cu}(μ 2 -L2) 2 ] n (CP7, X = Br, and CP8, X = Cl) resulting from treatment of 2-methyl-1,3 dithiane (L2) with CuBr and CuCl are isostructural with their CuI homologue [{Cu(μ 2 -I) 2 Cu}(μ 2 -L2) 2 ] n (CP5), reported previously. Using CuCN, a 2D CP of composition [{Cu(μ 2 -CN) 2 Cu}(μ 2 -L2) 2 ] n (CP9) has been isolated. Complexation of 2-isobutyl-1,3-dithiane (L3) on CuI generates a 2D material [{Cu 3 (μ 3 -I)(μ 2 -I) 2 (μ 2 -L3) 2 }] n (CP10), incorporating the usual trinuclear μ 3 -I-capped Cu clusters as SBUs, whereas 2D-polymeric compounds [{Cu(μ 2 -Br) 2 Cu}(μ 2 -L3) 2 ] n (CP11) and [{Cu(μ 2 -Cl) 2 Cu}(μ 2 -L3) 2 ] n (CP12) were obtained with CuBr and CuCl. Treatment of 2-Me 3 Si-1,3-dithiane (L4) with CuX yields the series [{Cu 2 (μ 4 -X)(μ 2 -X)}(μ 2 -L4)] n (CP13-CP15). With 2-phenyl-1,3-dithiane (L5), the outcome of the reaction with CuI depends on the reaction conditions. Reaction with CuI in MeCN provides a 1D ribbon [{Cu(μ 2 -I) 2 Cu}(MeCN) 2 (μ 2 -L5) 2 ] n (CP16), whereas treatment of CuI with L5 in hot EtCN yields 2D-polymeric[{Cu 3 (μ 3 -I)(μ 2 -I) 2 (μ 2 -L5) 2 }] n (CP17). A reversible phase transition from triclinic P1̅ to monoclinic P2 1 / m is observed when recording the structure of CP16 at five different temperatures in the 100-300 K range. Ligand L6 containing a ferrocenyl function at the 2-position was also probed as organometallic dithioether ligand. Reaction of L6 with 1 equiv of CuI produces the 0D dinuclear complex [{Cu(μ 2 -I) 2 Cu}(η 1 -L6) 2 (MeCN) 2 ] (D1), whereas treatment with 2 equiv of CuI affords the novel 1D CP [{Cu(μ 3 -I) 2 Cu}(μ-L6)] n (CP18), in which both S atoms of one L6 molecule span two copper centers of the infinite (CuI) n ribbon. Some selected results of thermal analyses and luminescence measurements are also presented.

In the quest for new heterocyclic scaffolds exhibiting potentially biological activities for medicinal chemistry, a multicomponent 1,3-dipolar cycloaddition reaction of tetrahydroisoquinolinium N -ylides, generated in situ from cyclic diketones and isoquinoline, and ( E )-3-arylidene-1-phenyl-pyrrolidine-2,5-diones has been developed. This route provides workable access to dispiropyrrolo[2,1- a ]isoquinoline-fused pyrrolidine-2,5-diones bearing two adjacent spiro-carbons. An unprecedented regioselectivity was observed in this 1,3-dipolar cycloaddition, leading to the construction of a novel dispirooxindole skeleton. The structure and relative stereochemistry of the spiranic adducts have been confirmed by three X-ray diffraction studies. To reinforce the observed regio- and stereoselectivity of the [3+2] cycloaddition, calculations using the DFT approach at the B3LYP/6-31G(d,p) level were carried out. It was found that this reaction affords the kinetic products., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Based on N-acyliminium species, two efficient and rapid approaches to diversify spirocyclic systems connected by two different carbon centers to the isoindole ring have been developed. The imide reduction and the tandem oxidative cleavage of olefin/formyl-amide equilibration were at first selected as the key steps for these strategies. Ultimately the intramolecular α-amidoalkylation reaction was achieved through the arylation of α-acetoxy lactams or α-hydroxy lactams using, respectively, a Lewis acid or a Brønsted acid depending on the nature of N-acyliminium precursors. The latter led, in addition to the spiro-6-membered aza-heterocycles, to the formation of scarce spiro-5-membered analogues which show promising inhibitory activities on human farnesyltransferase in the nanomolar range demonstrating improved IC50 values of up to 1.5 nM.

The first synthetic access to stable and acyclic 1,3-butadienes with two electron-withdrawing carbonyl groups and their potential to deliver new molecular scaffolds through intriguing endo-selective Diels-Alder cycloadditions are presented. The bicyclic scaffolds produced through the cycloaddition chemistry of electron-deficient dienes afforded potent Hedgehog signaling pathway inhibitors., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A structurally unique and strongly luminescent nonporous 3D coordination polymer (CP) [Cu 8 I 8 (methyldithiane) 4 ] n , CP3, has been prepared in a quasi-anticipated manner from 2-methyl-1,3-dithiane, L1, and CuI. This CP incorporates an unprecedented Cu 8 I 8 cluster built upon two side-fused open cubanes. The crystal structure of CP3 has been determined at 100, 150, 200, 250, 300, 350, and 400 K to study the temperature dependence of the Cu···Cu distances. Two other topological 1D and 2D CPs isomers of formula [{Cu 2 I 2 }(L1) 2 ] n featuring dinuclear {Cu 2 (μ 2 -I) 2 } rhomboids were also obtained independently by control of the reaction conditions. These two CPs convert into CP3 in hot PrCN, thus indicating that this latter material is the thermodynamic product. While CP1 and CP2 are not emissive, CP3 exhibits an intense luminescence due to the incorporation of the octanuclear Cu 8 I 8 clusters as secondary building units within the network. The photophysical properties of CP3 have been investigated and rationalized by means of DFT and TDDFT computing. Furthermore, the thermal stability of these materials has been studied by ATG and DSC analyses. The Raman spectra of CP1-3 have been recorded in the solid state in the 50-500 cm -1 region.

Phytochemical studies of the seeds of the Cameroonian medicinal plant, Salacia staudtiana, resulted in the isolation and identification of five new cardenolides (1-5) as well as a new dihydro-β-agarofuran (9), along with eight known compounds. The structures of all compounds were elucidated by 1D/2D NMR, ESI-HRMS data and comparison with literature data. The relative configurations of the new compounds were defined by X-ray crystallography analysis, NOESY correlations and coupling constants. We evaluated their antibacterial efficacy against two commonly dispersed environmental strains of Escherichia coli and Bacillus subtilis, and two pathogenic strains of Staphylococcus aureus and Pseudomonas aeruginosa, compared to the standard antibiotics, streptomycin and gentamicin. Moreover, we assessed the antibacterial activity of the crude extract of the seeds in parallel to evaluate the plausible synergistic effects of the compounds in chemical defense of the seeds during germination and plant reproduction. The isolated compounds showed moderate antibacterial activities against the tested organisms. Compounds 1 and 3 and the crude extract exhibited distinct antibacterial activities against B. subtilis and S. aureus. The isolated compounds showed weak DPPH radical scavenging properties compared to the reference standard (Trolox). Our study lends evidence to the antibacterial chemical defense of S. staudtiana seeds by seed-borne compounds., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Herein we report the isolation and characterization of aminal intermediates in the organocatalytic α-chlorination of aldehydes. These species are stable covalent ternary adducts of the substrate, the catalyst and the chlorinating reagent. NMR-assisted kinetic studies and isotopic labeling experiments with the isolated intermediate did not support its involvement in downstream stereoselective processes as proposed by Blackmond. By tuning the reactivity of the chlorinating reagent, we were able to suppress the accumulation of rate-limiting off-cycle intermediates. As a result, an efficient and highly enantioselective catalytic system with a broad functional group tolerance was developed., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A novel enantioselective approach to the synthesis of a compound collection inspired by natural pyrrolizidine alkaloids was developed, employing an enantioselectively catalyzed 1,3-dipolar cycloaddition as the key step. The cycloadducts were obtained with excellent enantio- and diastereoselectivity. Biological evaluation of the resulting compound collection revealed that the compound class has multiple bioactivities, including activity against Plasmodium falciparum 3D7 and inhibition of Hedgehog signaling.

Seven new cardenolides, staudtianoside A-F (1-6) and staudtianogenin A (8), were isolated along with six known compounds from the stem bark of the Cameroonian medicinal plant Salacia staudtiana Loes. ex Fritsch. The structures were elucidated by means of ESI-HRMS and NMR spectroscopic methods and by comparison with literature data. The relative configurations of the new compounds were determined by X-ray diffraction analysis, NOESY correlation and coupling constants. We evaluated the antibacterial efficacy of the isolated compounds against two commonly dispersed environmental strains of Escherichia coli and Bacillus subtilis, as well as against two human pathogenic clinical strains of Staphylococcus aureus and Pseudomonas aeruginosa. Compounds 1, 2 and 8 exhibited marked antibacterial potencies against the clinically relevant P. aeruginosa that were comparable to the standard antibiotics. Compound 2 was also active against S. aureus and E. coli. Further, compounds 5 and 8 demonstrated efficacy against E. coli as well as B. subtilis. The structure-activity relationship of the tested compounds is discussed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Complexity-generating chemical transformations that afford novel molecular scaffolds enriched in sp 3 character are highly desired. Here, we present a highly stereoselective scaffold diversity synthesis approach that utilizes cascade double-annulation reactions of diverse pairs of zwitterionic and non-zwitterionic partners with 3-formylchromones to generate highly complex tetracyclic benzopyrones. Each pair of annulation partners adds to the common chroman-4-one scaffold to build two new rings, supporting up to four contiguous chiral centers that include an all-carbon quaternary center. Differently ring-fused benzopyrones display different biological activities, thus demonstrating their immense potential in medicinal chemistry and chemical biology research.

The title compound, trimeth-yl(tetra-hydro-furan-κ O )aluminium(III), [Al(CH 3 ) 3 (C 4 H 8 O)], is an addition product of tri-methyl-aluminium and tetra-hydro-furan (THF). Instead of a dimeric structure, which is very common for these types of compounds, a monomeric mol-ecular structure is observed. The C-Al-C angles in the mol-ecule are very different from the C-Al-C angles found in dimeric mol-ecular structures, leading to a different symmetry around the Al III atom. The reasons for these differences are discussed.

The active complexes of chiral N,N'-dioxide ligands with dysprosium and magnesium salts catalyze the hetero-Diels-Alder reaction between 2-aza-3-silyloxy-butadienes and alkylidene oxindoles to selectively form 3,3'- and 3,4'-piperidinoyl spirooxindoles, respectively, in very high yields and with excellent enantioselectivities. The exo-selective asymmetric cycloaddition successfully regaled the construction of sp 3 -rich and highly substituted natural-product-based spirooxindoles supporting many chiral centers, including contiguous all-carbon quaternary centers., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

For the first time, POSS-based coordination polymers (CPs) have been structurally characterized. These CPs were obtained in high yield via self-assembly reactions of thioether-functionalized polysilsesquioxanes with Cu I salts under mild conditions. Single crystal analyses revealed the formation of 3D networks incorporating different secondary building units (SBUs) as connection nodes. The nature of the -SAr functionality allows a fine-tuning of the cluster nuclearity, that is, butterfly-shaped Cu 2 X 2 or closed cubane-type Cu 4 I 4 cores. As such, the resulting hybrid materials exhibit a combination of high thermal stability arising from the inorganic POSS core along with interesting luminescent properties conferred by the cubane cluster core. Furthermore, the occurrence of channels has been shown crystallographically in the case of the Cu 4 I 4 cluster containing CP., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Described herein is a selective way to control the reaction of allylic amines with metalorganic bases depending on the amine handle as well as the metalorganic base is used. Depending on the number of coordinating groups within the amine handle either a selective carbometalation or deprotonation reaction can be performed. By changing the alkali metal within the base from lithium to either sodium or potassium, a change of chemoselectivity takes place and the reaction of piperidinoallylamine can be controlled., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A highly enantioselective copper-catalyzed vinylogous propargylic substitution has been developed. Aromatic and aliphatic propargylic esters react smoothly with substituted coumarins under mild reaction conditions to give the desired products with excellent yields and enantioselectivities. Subsequent single-step transformations enable the synthesis of a wide range of multifunctional and diverse compounds, and allow the efficient combination of different natural product fragments. Investigation of the obtained compound collection in cell-based assays monitoring changes in phenotype led to the discovery of a novel class of autophagy inhibitors., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We present the synthesis, structure, and exemplary reactivity of siloxides with a planar-chiral N,N-dimethylaminomethylferrocene backbone. Several zinc complexes based on the racemic as well as the enantiomerically pure silanol were synthesized in the presence of water and crystallographically characterized, and their behavior in solution was examined. The chiral probe present in this system is a valuable tool for identifying the structure in solution. Furthermore, the zinc siloxides exhibit a comparable reactivity to the corresponding silanols. Therefore, they can be regarded as "masked" silanols, especially when the silanols are preparatively inaccessible., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Selective cleavage of a silicon-carbon bond in tetraorganosilanes is still a great challenge. A new type of Si-C(sp 3 ) bond cleavage in bench-stable (aminomethyl)silanes with common organolithium reagents as nucleophiles has now been identified. Suitable leaving groups are benzyl, allyl, and phenylthiomethyl groups. A β-donor function and polar solvents are essential for the reaction. Simple switching between α-deprotonation and substitution is possible through slight modifications of the reaction conditions. The stereochemical course of the reaction was elucidated by using a silicon-chiral benzylsilane. The new transformation proceeds stereospecifically with inversion of configuration and can be used for the targeted synthesis of enantiomerically pure tetraorganosilanes, which are otherwise difficult to access. Quantum chemical calculations provided insight into the mechanism of the new substitution., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Extensive chemical investigation of the endophytic fungus, Fusarium solani JK10, harbored in the root of the Ghanaian medicinal plant Chlorophora regia, using the OSMAC (One Strain Many Compounds) approach resulted in the isolation of seven new 7-desmethyl fusarin C derivatives (1-7), together with five known compounds (8-12). The structures of the new compounds were elucidated by analysis of their spectroscopic data including 1D, 2D NMR, HRESI-MS n and IR data. The relative configuration of compounds 1/2 was deduced by comparison of their experimental electronic circular dichroism (ECD) and optical rotation data with those reported in literature. The absolute configuration of solaniol (10), a known compound with undefined absolute stereochemistry, was established for the first time by X-ray diffraction analysis of a single-crystal structure using Cu-Kα radiation. The antibacterial activities of the crude fungal extract and the compounds isolated from the fungus were evaluated against some clinically important bacterial strains such as Staphylococcus aureus and Bacillus subtilis, as well as an environmental strain of Escherichia coli and the soil bacterium Acinetobacter sp. BD4. Compounds 3/4 and 6 exhibited antibacterial efficacies against the soil bacterium Acinetobacter sp., comparable to the reference standard streptomycin. All the tested compounds (1-9) demonstrated antibacterial activity against the environmental strain of E. coli, whereas no antibacterial activity was observed against S. aureus and B. subtilis. The antibacterial activity of the isolated compounds typically against E. coli and Acinetobacter sp. provides further insight into the possible involvement of root-borne endophytes in chemical defense of their host plants in selected ecological niches., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The reaction of benzyl lithiums is an important aspect in organic and organometallic synthesis. Reported herein are detailed insights into the reactivity of benzyl lithiums as regulated by intermediate structures. By discussing the carbometalation of allylamines and the reaction of the formed benzyl-lithium compounds with electrophiles, the influence of the metal as well as the solvent on the electronic structure of the intermediate is described. This molecular structure strongly influences the reactivity of these intermediates. By choosing the appropriate reaction conditions, the regioselectivity of reactions with electrophiles can be regulated. With trimethylchlorosilane in n-pentane a selective reaction at the para-position takes place. In contrast, selective reaction at the benzylic position, with trimethylchlorostannane in tetrahydrofuran (THF) as a solvent, is accomplished., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An endophytic fungus, Eupenicillium sp. LG41, isolated from the Chinese medicinal plant Xanthium sibiricum, was subjected to epigenetic modulation using an NAD + -dependent histone deacetylase (HDAC) inhibitor, nicotinamide. Epigenetic stimulation of the endophyte led to enhanced production of two new decalin-containing compounds, eupenicinicols C and D (3 and 4), along with two biosynthetically related known compounds, eujavanicol A (1) and eupenicinicol A (2). The structures and stereochemistry of the new compounds were elucidated by extensive spectroscopic analysis using LC-HRMS, NMR, optical rotation, and ECD calculations, as well as single-crystal X-ray diffraction. Compounds 3 and 4 exist in chemical equilibrium with two and three cis/trans isomers, respectively, as revealed by LC-MS analysis. Compound 4 was active against Staphylococcus aureus with an MIC of 0.1 μg/mL and demonstrated marked cytotoxicity against the human acute monocytic leukemia cell line (THP-1). We have shown that the HDAC inhibitor, nicotinamide, enhanced the production of compounds 3 and 4 by endophytic Eupenicillium sp. LG41, facilitating their isolation, structure elucidation, and evaluation of their biological activities.

Chemical investigation of Aspergillus japonicus CAM231, isolated from the leaf of Garcina preussii collected in Cameroon, yielded two new compounds; one pyrone derivative, hydroxy neovasinin (1) and one phenol derivative, asperolan (2), together with two known compounds neovasifurarone B (3) and variecolin (4). The structures of the two new compounds were established using intensive NMR spectroscopy and HRMS spectra in comparison with data found in literature. The structure of compound 1 was confirmed by single-crystal X-ray crystallographic analysis in combination with NOESY experiment. The new compounds were screened for their cytotoxic and antibacterial properties; however, the tested compounds displayed no significant activities.

The selective transformation of different starting materials by different metal catalysts under individually optimized reaction conditions to structurally different intermediates and products is a powerful approach to generate diverse molecular scaffolds. In a more unified albeit synthetically challenging strategy, common starting materials would be exposed to a common metal catalysis, leading to a common intermediate and giving rise to different scaffolds by tuning the reactivity of the metal catalyst through different ligands. Herein we present a ligand-directed synthesis approach for the gold(I)-catalysed cycloisomerization of oxindole-derived 1,6-enynes that affords distinct molecular scaffolds following different catalytic reaction pathways. Varying electronic properties and the steric demand of the gold(I) ligands steers the fate of a common intermediary gold carbene to selectively form spirooxindoles, quinolones or df-oxindoles. Investigation of a synthesized compound collection in cell-based assays delivers structurally novel, selective modulators of the Hedgehog and Wnt signalling pathways, autophagy and of cellular proliferation.

A silver-catalyzed highly enantioselective 1,3-dipolar cycloaddition reaction of α-silylimines with pyrone-based trisubstituted olefins was developed affording bi- and tricyclic α-quaternary-carbon-rich pyrano-pyrrolidines in excellent yields. The tricyclic benzopyrone adducts thus obtained were efficiently transformed into highly complex tetracyclic scaffolds supporting four consecutive stereogenic centers with three quaternary carbons., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Iridoids comprise a large group of monoterpenoid natural products displaying a diverse array of biological activities ranging from neurotrophic to anti-inflammatory and anti-tumorigenic properties. Therefore, the development of concise synthesis routes to compound collections inspired by the structural features of these natural products is of particular relevance for chemical biology and medicinal chemistry. Herein we describe a samarium diiodide-mediated synthesis of a small, focused iridoid-inspired compound collection. Characterization of these iridoid analogues in biological assays revealed novel small-molecule inhibitors of autophagy.

The title compounds, [Sn 3 (CH 3 ) 9 (OH) 2 (H 2 O) 2 ][Sn(CH 3 ) 3 (CHO 2 ) 2 ] ( 1 ) and [Sn 3 (CH 3 ) 9 (OH) 2 ]Cl·H 2 O ( 2 ), are partially condensed products of hydrolysed tri-methyl-tin chloride. In the structures of 1 and 2 , short cationic tris-tannatoxanes (C 9 H 29 O 2 Sn 3 ) are bridged by a diformatotri-methyl-tin anion or a chloride anion, respectively. Hydrogen bridges are present and supposedly stabilize these structures against further polymerization to the known polymeric tri-methyl-tin hydroxide. Especially noteworthy is that the formate present in this structure was formed from atmospheric CO 2 .

EtS(CH 2 ) 4 SEt, L1, forms with CuI a luminescent 2D polymer [Cu 4 I 4 {μ-L1} 2 ] n (CP1), which exhibits no triplet excitation energy migration, but with CuBr, it forms a 3D material (CP2), [(Cu 2 Br 2 ){μ-L1}] n consisting of parallel (Cu 2 Br 2 S 2 ) n layers bridged by L1's. CP2 shows T 1 -T 1 annihilation at 298 K but not at 77 K.

Catalytic addition of chiral phosphine, that is, (R)- or (S)-SITCP, to an α-substituted allene ester generated a zwitterionic dipole. Under optimized reaction conditions, this dipole could engage isatine-derived N-Boc-ketimines in a novel mode of [3+2] annulation reaction. Pyrrolinyl spirooxindoles are thus afforded in high yields and with excellent enantioselectivities. The unprecedented annulation reaction successfully facilitated the construction of sp(3) -rich and highly substituted 3,2'-pyrrolidinyl spirooxindoles supporting many chiral centers., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An efficient strategy has been established for the enantiodivergent synthesis of natural product inspired compounds embodying both tropane and pyrrolidine natural product fragments. This strategy includes the enantioselective kinetic resolution of racemic tropanes by means of a copper(I)-catalyzed [3+2] cycloaddition and allows the preparation of two enantiopure products in a one-pot reaction in high yield and with high diastereo- and enantioselectivity by using one chiral catalyst., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The catalytic addition of the amino acid derived bifunctional N-acylaminophosphine to an α-substituted allene ester generated a zwitterionic dipole that engaged the vinylogous ester function of 3-cyano-chromones in a [4 + 2] annulation reaction to deliver tetrahydroxanthones embodying three consecutive chiral centers in high yields and with excellent enantioselectivities. The established asymmetric synthesis further paves the way to two different classes of complex, sp(3)-rich tetracyclic benzopyrans via efficient cascade reactions.

Three new compounds, colletotrichones A-C (1-3), and one known compound, chermesinone B (4a), were isolated from an endophytic fungus, Colletotrichum sp. BS4, harbored in the leaves of Buxus sinica, a well-known boxwood plant used in traditional Chinese medicine (TCM). Their structures were determined by extensive spectroscopic analyses including 1D and 2D NMR, HRMS, ECD spectra, UV, and IR, as well as single-crystal X-ray diffraction, and shown to be azaphilones sharing a 3,6a-dimethyl-9-(2-methylbutanoyl)-9H-furo[2,3-h]isochromene-6,8-dione scaffold. Owing to the remarkable antibacterial potency of known azaphilones coupled to the usage of the host plant in TCM, we evaluated the antibacterial efficacy of the isolated compounds against two commonly dispersed environmental strains of Escherichia coli and Bacillus subtilis, as well as against two human pathogenic clinical strains of Staphylococcus aureus and Pseudomonas aeruginosa. Compound 1 exhibited marked antibacterial potencies against the environmental strains that were comparable to the standard antibiotics. Compound 3 was also active against E. coli. Finally, compound 2a exhibited the same efficacy as streptomycin against the clinically relevant bacterium S. aureus. The in vitro cytotoxicity of these compounds on a human acute monocytic leukemia cell line (THP-1) was also assessed. Our results provide a scientific rationale for further investigations into endophyte-mediated host chemical defense against specialist and generalist pathogens.

The title compound, C17H24N2O3S, was synthesized in order to determine the relative configuration of the corresponding β-keto aldehyde. In the U-shaped mol-ecule, the five-membered ring approximates an envelope, with the methyl-ene C atom adjacent to the quaternary C atom being the flap, and the methyl and isopropyl substituents lying to the same side of the ring. The dihedral angles between the four nearly coplanar atoms of the five-membered ring and the flap and the aromatic ring are 35.74 (15) and 55.72 (9)°, respectively. The bond angles around the S atom are in the range from 103.26 (12) to 120.65 (14)°. In the crystal, mol-ecules are linked via N-H⋯O hydrogen bonds, forming a chain along the a axis.

The title compound, [Cu2I2(C11H22N2)2], crystallizes as a symmetric dimer with one quarter of the mol-ecule in the asymmetric unit. The copper(I) atom, the iodine atom and the central methyl-ene C atom of the di(piperidin-1-yl)methane ligand lie on a mirror plane and the complete molecule exhibits point group symmetry 2/m. To the best of our knowledge it is the first di-amine copper(I) complex containing a four-membered chelate ring. Compared to other di-amine copper(I) iodide dimers, the title compound has a short Cu⋯Cu distance of 2.5137 (11) Å, but a long Cu-N bond length of 2.213 (3) Å. The I-Cu-I angle [121.84 (2)°] is large, and the N-Cu-N angle = 66.61 (13)° is the smallest one found for copper(I) di-amine complexes. As a result of the four-membered ring, the ligands around the copper(I) atom have an extremely distorted tetra-hedral arrangement. In the crystal, there are no significant inter-molecular inter-actions present.

The title compound, [Cu2I2(CH3CN)4], exhibits a centrosymmetric Cu2I2 core [Cu⋯Cu distance = 2.7482 (11) Å], the Cu(I) atoms of which are further coordinated by four mol-ecules of aceto-nitrile. The Cu(I) atom has an overall distorted tetra-hedral coordination environment evidenced by L-Cu-L angles (L = N or I) ranging from 100.47 (10) to 117.06 (2)°. The coordination geometries of the aceto-nitrile ligands deviate slightly from linearity as shown by Cu-N-C angles of 167.0 (2) and 172.7 (2)°. In the crystal, there are no significant hydrogen-bonding inter-actions present, so the crystal packing seems to be formed predominantly by van der Waals forces.

With the aim to develop new potent antitubercular agents, a series of novel dispirooxindolopyrrolidines and dispirooxindolopyrrolothiazoles have been synthesized via a three-component 1,3-dipolar cycloaddition of (Z)-3-arylidenebenzofuran-2-ones, substituted isatin derivatives and α-aminoacids. The stereochemistry of the spiroadducts has been confirmed by an X-ray diffraction analysis. All the target heterocycles were evaluated for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv strain and the most active compounds were subjected to cytotoxicity studies against (RAW 264.7) cell lines. Among them, twelve compounds showed potent anti-tubercular activity with MIC ranging from 1.56 to 6.25 μg/mL. In particular dispirooxindolopyrrolothiazole derivatives 5c and 5f were found to be the most active (MIC of 1.56 μg/mL) with a good safety profile (27.53% and 20.74% at 50 μM, respectively). This is the first report demonstrating the benzofuranone oxindole hybrids as potential antimycobacterial agents., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A series of original spiropyrrolizidine derivatives has been prepared by a one-pot three-component [3 + 2] cycloaddition reaction of (E)-3-arylidene-1-phenyl-pyrrolidine-2,5-diones, l-proline, and the cyclic ketones 1H-indole-2,3-dione (isatin), indenoquinoxaline-11-one and acenaphthenequinone. We disclose an unprecedented isomerization of some spiroadducts leading to a new family of spirooxindolepyrrolizidines. Furthermore, these cycloadducts underwent retro-1,3-dipolar cycloaddition yielding unexpected regioisomers. Upon treatment of the dipolarophiles with in situ generated azomethine ylides from l-proline or acenaphthenequinone, formation of spiroadducts and unusual polycyclic fused piperazines through a stepwise [3 + 3] cycloaddition pathway is observed. The stereochemistry of these N-heterocycles has been confirmed by several X-ray diffraction studies. Some of these compounds exhibit extensive hydrogen bonding in the crystalline state. To enlighten the observed regio- and stereoselectivity of the [3 + 2] cycloaddition, calculations using the DFT approach at the B3LYP/6-31G(d,p) level were carried out. It was found that this reaction is under kinetic control.