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New Ligands (new + ligand)
Selected AbstractsAn Expedient Synthesis of Perfluorinated Tetraazamacrocycles: New Ligands for Copper-Catalyzed Oxidation under Fluorous Biphasic ConditionsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 20 2006Augustin de Castries Abstract Conjugate additions of cyclam to perfluorohexyl vinyl sulfone and sulfoxide, which act as efficient fluorous Michael acceptors, readily give access to new fluoro-ponytail tetraazamacrocycles in good yields. The solubility of the N -tetrasubstituted macrocycles depends dramatically on the nature of the polar function (SO or SO2): the sulfoxide cyclam derivative is soluble in perfluorodecaline (pfd) and perfluoromethylcyclohexane (pfmc) while the sulfonyl derivative is almost insoluble in organic or fluorous solvents. In agreement with the well known affinity of cyclam for copper(II) ions, stable copper complexes of the fluorous macrocyclic ligands have been isolated and characterized. In chloroform/methanol, complexes with four perfluorinated tails have been obtained from reaction of the tetra- N -perfluorohexylsulfinyl-substituted macrocycle with copper nitrate and copper perfluorocarboxylate. In trifluoroethanol, a selective retro-Michael reaction has been observed and the same reaction specifically gives copper complexes of the tri- N -substituted macrocycle. Complexes with three and four fluorous tails associated with perfluorocarboxylate counteranions are soluble in fluorous solvents (pfd and pfmc). These copper complexes were tested as catalysts for the oxidation of cyclohexene by molecular oxygen in the presence of tert -butyl hydroperoxide (tbhp). The oxidation reactions proceed under fluorous biphasic conditions and the catalyst can be recovered and reused. Quenching experiments indicate that cyclohexenyl hydroperoxide is the main oxidation product of the reaction performed with or without tbhp. Interestingly, these perfluorinated copper complexes are good, recyclable catalysts for the oxidation of cyclohexene by molecular oxygen without tbhp at room temperature and 65 °C.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Cymantrene-Derived Monodentate Phosphites: New Ligands for Rh-Catalyzed Enantioselective Hydrogenation.CHEMINFORM, Issue 19 2007Sergey E. Lyubimov Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Diastereoselective Synthesis of Thieno[3,,2,:4,5]cyclopenta[1,2-d][1,3]oxazolines , New Ligands for the Copper-Catalyzed Asymmetric Conjugate Addition of Diethylzinc to Enones.CHEMINFORM, Issue 7 2005Bianca Flavia Bonini Abstract For Abstract see ChemInform Abstract in Full Text. [source] Samarium-Promoted Coupling of 1,10-Phenanthroline with Carbonyl Compounds for Synthesis of New Ligands.CHEMINFORM, Issue 33 2004Jeremy A. Weitgenant Abstract For Abstract see ChemInform Abstract in Full Text. [source] Novel RuII Complexes with Bispidine-Based Bridging Ligands: Luminescence Sensing and Photocatalytic PropertiesEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 8 2010Christoph Busche Abstract New ligands with a bidentate bipyridyl (bpy) and a tetradentate bispidine (bisp) subunit (bipyridyl = 2,2,-bipyridine derivative, bispidine = 3,7-diazabicyclo[3.3.1]nonane derivative) and their heterodinuclear {[Ru(bpy)3]2+ -[M(bisp)]2+} complexes (M = Cu2+, Fe2+) were prepared and characterized. The luminescence of the mononuclear RuII complexes (metal-free bisp subunit) is efficiently quenched in presence of CuII. An EPR spectroscopic study reveals thatvisible light irradiation does not alter the oxidation states of the two metal ions in {[Ru(bpy)3]2+ -[Cu(bisp)]2+}, i.e. there is energy rather than electron transfer. The heterodinuclear {[Ru(bpy)3]2+ -[Cu(bisp)]2+} complex shows a significantphotocatalytic activity in the aziridination of styrene. [source] Design of Neutral Metallomesogens from 5,5-Dimethyldipyrromethane: Metal Ion Mediated Control of Folding and Hairpin StructuresEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 32 2008Kelly A. Ames Abstract New ligands derived from 5,5-dimethyldipyrromethane and their corresponding neutral complexes with ZnII and PdII are described. The ligands incorporate either a hexacatenar [H2(1n), n = 1, 10, 12, 14 and 16], tetracatenar [H2(2n), n = 1 and 16] or an extended dicatenar structure [H2(3n), n = 1and 16]. Single-crystal X-ray structure determinations of [Zn2(11)2] and [Zn2(31)2] confirm a distorted tetrahedral geometry at ZnII to afford double-stranded helical structures, while the PdII species [Pd(31)] shows a distorted square-planar geometry with the ligand adopting an alternative hairpin conformation. The metal-free hexacatenar ligands H2(1n) (n = 10, 12, 14, 16) and the corresponding complexes [Zn2(116)2] and [Pd(1n)] (n = 12, 14, 16) are not mesomorphic. However, the tetracatenar complex [Zn2(216)2] generates a smectic mesophase, as confirmed by X-ray diffraction, while [Pd(216)] and the metal-free ligand H2(216) show no mesomorphic behaviour. Two of the extended dicatenar compounds, H2(316) and [Zn2(316)2] are non-mesomorphic, while [Pd(316)] displays a smectic A phase.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] New ligands for the Fe(III)-mediated reverse atom transfer radical polymerization of methyl methacrylateJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 9 2006Gang Wang Abstract A series of (di)picolinic acids and their derivates are investigated as novel complexing tridentate or bidentate ligands in the iron-mediated reverse atom transfer radical polymerization of methyl methacrylate in N,N -dimethylformamide at 100 °C with 2,2,-azobisisobutyrontrile as an initiator. The polymerization rates and polydispersity indices (1.32,1.8) of the resulting polymers are dependent on the structures of the ligands employed. Different iron complexes may be involved in iron-mediated reverse atom transfer radical polymerization, depending on the type of acid used. 1H NMR spectroscopy has been used to study the structure of the resulting polymers. Chain-extension reactions have been performed to further confirm the living nature of this catalytic system. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 2912,2921, 2006 [source] A New Pentadentate Ligand Forms Both a Di- and a Mononuclear MnII Complex: Electrochemical, Spectroscopic and Superoxide Dismutase Activity StudiesEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 28 2007Federico Cisnetti Abstract The X-ray crystal structure of the dinuclear complex[1(PF6)2] derived from a new ligand bearing both imidazole and phenolato moieties, namely N -(2-hydroxybenzyl)- N,N,-bis[2-(N -methylimidazolyl)methyl]ethane-1,2-diamine (LH), is described and its properties in organic solvent (CH3CN) investigated (EPR, electrochemistry). [1(PF6)2] is shown to be a mononuclear MnII species in aqueous solution and displays an efficient SOD-like activity, as measured by the McCord,Fridovich assay performed both in conventional phosphate buffer and in a noncoordinating buffer (PIPES). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] A Zig-Zag [MnII4] Cluster from a Novel Bis(,-diketonate) LigandEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 10 2006Guillem Aromí Abstract A new ligand, H5L3, has been synthesized featuring seven linearly arranged oxygen donors in form of two 1,3-diketone and three phenol groups. The X-ray structure of H5L3 unveils a rare case where one of the diketones is in the enolic form and the other one in the bis(carbonyl) form. This structure is shown by 1H NMR to persist in solution. Reaction of H5L3 with Mn(AcO)2 in pyridine leads to the novel tetranuclear cluster [Mn4(H2L3)2(OAc)2(py)5] (1), which displays an unusual core in form of a zig-zag chain. Bulk magnetic measurements revealed the existence of weak antiferromagnetic coupling within the molecule. Numerical fits to a model described by the Hamiltonian H = ,2J1(S1S2 + S3S4) , 2J2(S2S3) yield coupling constants of J1 = ,2.23 cm,1, J2 = ,0.85 cm,1 and g = 2.08. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Molecular Tectonics: Design of 1-D Coordination Networks Based on Pyrene-Bearing Pyrazolyl UnitsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 1 2003Abdelaziz Jouaiti Abstract The synthesis of a new ligand based on a pyrene backbone bearing four pyrazolyl units is reported. Whereas this compound forms a discrete exo-binuclear complex with palladium, in the presence of silver a 1-D coordination network is obtained and structurally characterised in the solid state by X-ray diffraction method. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Synthesis and Hormonal Activity of the (25S)-Cholesten-26-oic Acids , Potent Ligands for the DAF-12 Receptor in Caenorhabditis elegansEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 22 2009René Martin Abstract Using a highly stereoselective Evans aldol reaction for the introduction of the stereogenic center at C-25, we describe an efficient synthesis of the orthogonally diprotected (25S)-26-hydroxycholesterol 11. In a few synthetic steps, this crucial intermediate 11 has been converted into the four (25S)-cholesten-26-oic acids 1,4, which have been obtained in 12,15 steps and 19,53,% overall yield based on commercially available 3,-hydroxychol-5-en-24-oic acid (5). Our biological studies of the compounds 1,4 reveal that (25S)-,7 -dafachronic acid (1) represents the most active steroidal ligand for the hormonal receptor DAF-12 in Caenorhabditis elegans. Moreover, the saturated (25S)-dafachronic acid (3) represents a new ligand for this receptor and the (25S)-steroidal acids are more active as compared to their corresponding (25R)-counterparts.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] First Heterogeneous Ligand- and Salt-Free Larock Indole SynthesisADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 13 2009Nelly Batail Abstract A new ligand- and salt-free procedure using heterogeneous palladium catalysts for the Larock indole and benzofuran synthesis is reported. After optimisation of the reaction conditions, good to high isolated yields have been achieved for a variety of structures. Recycling studies have shown that the palladium catalysts can be readily recovered and reused. Reactions and recovery of the palladium catalysts can be carried out in the presence of air, without any particular precaution. [source] An Inexpensive and Efficient Copper Catalyst for N -Arylation of Amines, Amides and Nitrogen-Containing HeterocyclesADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 15 2006Xun Guo Abstract An inexpensive and efficient catalyst system has been developed for the N -arylation of nitrogen-containing compounds including a variety of amines, amides, indole and imidazole. This simple protocol uses CuI as the catalyst, commercial available pipecolinic acid as the new ligand, K2CO3 as the base and DMF as the solvent. [source] The synthesis and application of 2-acetyl-6-(1-naphthyl)-pyridine oxime as a new ligand for palladium precatalyst in Suzuki coupling reactionJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 1 2009Yongchang Zhou The synthesis of 2-acetyl-6-(1-naphthyl)-pyridine oxime ligand from 2,6-dibromopyridine and 1-bromo-naphthalene is described, and the new palladium(II) complex used as a Pd(0) precatalyst in the Suzuki cross-coupling reaction was studied. The results showed that the novel naphthalene pyridine oxime complex could serve as an efficient precatalyst. J. Heterocyclic Chem., 46, 116 (2009). [source] Adsorption of Cadmium Ion and Gallium Ion to Immobilized Metallothionein Fusion ProteinBIOTECHNOLOGY PROGRESS, Issue 6 2002Masaaki Terashima A fusion protein made from maltose binding protein (pmal) and human metallothionein (MT) was expressed using E. coli. The purified recombinant protein (pmal-MT) was immobilized on Chitopearl resin, and characteristics of pmal-MT for metal binding were evaluated. As expected from the tertiary structure of metallothionein, the pmal-MT ligand adsorbed 12.1 cadmium molecules per one molecule of the ligand at pH 5.2. The pmal-MT ligand also bound 26.6 gallium molecules per one molecule of the ligand at pH 6.5. Neither cadmium ion nor gallium ion bound to a control protein bovine serum albumin (BSA). Adsorption isotherms for both ions were correlated by Langmuir-type equations. Two types of binding sites have been elucidated on the basis of HSAB (hard and soft acid and base) theory. It was suggested that gallium ion specifically binds to amino acid residues containing oxygen and nitrogen atoms, while cadmium ion binds to specific binding sites formed by multiple cysteine residues. The pmal-MT ligand bound these metals in the concentration range of 0.2,1.0 mM, and the bound metal ions could be eluted under relatively mild conditions (pH 2.0). The pmal-MT Chitopearl resin was stable and could be used repeatedly without loss of binding activity. Thus, this new ligand would be useful for recovery of toxic heavy metals and/or valuable metal ions from various aqueous solutions. [source] A New Fluorimetric Reagent for Determination of Trace Amounts of EuropiumCHINESE JOURNAL OF CHEMISTRY, Issue 9 2002Peng Lin Abstract In this paper, a new ligand, 2, 9-bis [N, N -bis (carboxymethyl) -aminomethyl] ,1, 10-phenanthroline, was synthesized and used to establish a novel fluorimetric method for the determination of trace amounts of europium. The fluorescence intensity was a linear function of the concentration of europium in the range,of 4.0 × 10,9,1.0 × 10,6 mol/L. The detection limit was 1.0 × 10,9 mol/L. The standard addition method was used to determine the europium in a synthetic rare-earth sample and high purity Y2O3 matrix with satisfactory results. [source] Norbornene Bidentate Ligands: Coordination Chemistry and Enantioselective Catalytic ApplicationsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 5 2010Fernando Fernández Abstract N - and P-donor derivatives have been prepared by functionalization of a readily available norbornene precursor. Palladium catalytic systems containing these new ligands were applied in allylic substitution, and yielded high activities and excellent enantioselectivities for the allylic alkylation and amination reactions (ee up to 97,%). A full coordination analysis of the catalytic precursors including modelling studies was also carried out. [source] Expanding the Range of "Daniphos"-Type P,P- and P,N-Ligands: Synthesis and Structural Characterisation of New [(,6 -arene)Cr(CO)3] ComplexesEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 31 2007Elisabetta Alberico Abstract New P,P- and P,N-ligands have been synthesised whose core structure is an [(,6 -arene)Cr(CO)3] unit. These new ligands, which extend the range of "Daniphos" ligands, are endowed with central and planar chirality and have been prepared through a stereoselective synthetic strategy from optically pure benzylamines bearing a second substituent on the arene other than the benzyldimethylamino group. Because the two faces of unsymmetrically 1,2- and 1,3-disubstituted benzylamine are diastereotopic, which means that diastereomeric complexes arise upon coordination of theCr(CO)3 fragment to either of these two faces, the synthetic plan has been adjusted by exploiting the trimethylsilyl group as a temporary steric modulator in order to access both complexes with high diastereoselectivity. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Fine-Tuning Ligands for Catalysis Using Supramolecular StrategiesEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 29 2007Vincent F. Slagt Abstract Coordinative bonds have been used to prepare supramolecular ligands leading to well-defined catalysts formed by assembly. The construction of these ligands is based on selective metal,ligand interactions between nitrogen donor atoms of phosphorus-nitrogen building blocks and various zinc(II) porphyrins. The major advantage of this supramolecular approach of catalyst preparation is the simplification of ligand variation enabling straightforward modification of steric, electronic and chiral properties of the supramolecular ligand. A large number of new ligands becomes accessible by this modular variation of the building blocks. The ligand assembly based on pyridyl phosphites and zinc(II) porphyrin with electron-withdrawing substituents led to a twelve-fold increase in activity and an increase in enantioselectivity from 17 to 50,% in the rhodium-catalyzed hydrogenation of dimethyl itaconate. The first examples of assemblies based on non-chiral ligands and chiral zinc(II) porphyrin template molecules show, as proof of principle, an enantiomeric excess up to 18,% in the asymmetric palladium-catalyzed allylic alkylation. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Synthesis and Transition Metal Complexes of Novel N,N,O Scorpionate Ligands Suitable for Solid Phase ImmobilisationEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 24 2006Eike Hübner Abstract Introduction of an allyl or a hydroxymethyl group to bis(3,5-dimethylpyrazol-1-yl)acetic acid (1) at the bridging carbon atom leads to the new tripodal N,N,O ligands 2,2-bis(3,5-dimethylpyrazol-1-yl)pent-4-enoic acid (Hbdmpzpen) (2) and 2,2-bis(3,5-dimethylpyrazol-1-yl)-3-hydroxypropionic acid (Hbdmpzhp) (3). These ligands exhibit similar chemical behaviour to that of 1, but they have the additional possibility to be immobilised to a solid phase. Esterification of the hydroxymethyl linker of 3 yields 2,2-bis(3,5-dimethylpyrazol-1-yl)-3-acetatopropionic acid (Hbdmpzap) (4). The molecular structures of 2, 3 and 4 all exhibit intramolecular hydrogen bridges. Introduction of a hydroxymethyl group to methyl bis(3,5-dimethylpyrazol-1-yl)acetate (5) yields methyl2,2-bis(3,5-dimethylpyrazol-1-yl)-3-hydroxypropionate(Mebdmpzhp) (6), which can be immobilised on Merrifield polymer to yield modified resin P - 6. To investigate the reactivity of these new ligands, manganese and rhenium complexes of 2, 3 and 4 have been studied. The molecular structures of the two manganese complexes [Mn(bdmpzpen)(CO)3] (7) and [Mn(bdmpzap)(CO)3] (8) have been confirmed by single-crystal X-ray structure determination. Saponification of polymer resin P - 6 and subsequent reaction with [ReBr(CO)5] yields rhenium tricarbonyl complexes anchored on Merrifield polymer (P -Re). Solid phase immobilisation of the [Mn(bdmpzpen)(CO)3] (7) and [Re(bdmpzpen)(CO)3] (9) complexes on 3-mercaptopropyl functionalised silica is initialised by AIBN. The tripodal coordination of manganese and rhenium in these functionalised Merrifield resins (P -Re) and silica (S -Mn, S -Re) is proven by a single A1 and two E signals in the IR spectra that are typical for unsymmetrical "piano stool" type carbonyl complexes. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Sulfilimines and Sulfoximines by Reaction of Nitriles with Perfluoroalkyl SulfoxidesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 19 2009Yohan Macé Abstract The species obtained by activation of perfluoroalkylated sulfoxides with trifluoromethanesulfonic anhydride behaves as highly electrophilic entities. Their reaction with nitriles allows a Ritter-like process leading to the new fluorinated acylsulfilimines 1,21 after hydrolysis. This flexible methodology allows some variation of both the sulfoxide and nitrile components. Derived acylsulfoximines 22,25 or free sulfoximines 26,28 could be selectively obtained, as needed, by further controlled oxidation with the cheap and nontoxic potassium permanganate. This oxidation may be performed either after isolation of the intermediate sulfilimine, or more conveniently in a one-pot process directly from fluorinated sulfoxides. This versatile, solvent and metal free, reaction is thus an opening way through the synthesis of new ligands or electrophilic trifluoromethylating reagents.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Tetranectin binds hepatocyte growth factor and tissue-type plasminogen activatorFEBS JOURNAL, Issue 8 2003Uffe B. Westergaard In the search for new ligands for the plasminogen kringle 4 binding-protein tetranectin, it has been found by ligand blot analysis and ELISA that tetranectin specifically bound to the plasminogen-like hepatocyte growth factor and tissue-type plasminogen activator. The dissociation constants of these complexes were found to be within the same order of magnitude as the one for the plasminogen-tetranectin complex. The study also revealed that tetranectin did not interact with the kindred proteins: macrophage-stimulating protein, urokinase-type plasminogen activator and prothrombin. In order to examine the function of tetranectin, a kinetic analysis of the tPA-catalysed plasminogen activation was performed. The kinetic parameters of the tetranectin-stimulated enhancement of tPA were comparable to fibrinogen fragments, which are so far the best inducer of tPA-catalysed plasminogen activation. The enhanced activation was suggested to be caused by tetranectin's ability to bind and accumulate tPA in an active conformation. [source] Synthesis and Characterization of Dendrimeric Bridged Salen/Saloph Complexes and Investigation of Their Magnetic and Thermal BehaviorsHELVETICA CHIMICA ACTA, Issue 5 2010Ziya Erdem Abstract Eight new multinuclear FeIII and CrIII complexes involving the tetradentate Schiff bases N,N, -bis(salicylidene)ethylenediamine (salenH2) or N,N, -bis(salicylidene)benzene-1,2-diamine (salophH2) and the two new ligands 4,4,,4,,4,,,,4,,,,,4,,,,-[1,3,5-triazine-2,4,6-triyltris(nitrilomethylidyne-4,1-phenyleneoxy-1,3,5-triazine-6,2,4-triyldiimino)]hexakis[benzoic acid] (4) or 5,5,,5,,5,,,,5,,,,,5,,,,-[1,3,5-triazine-2,4,6-triyltris(nitrilomethylidyne-4,1-phenyleneoxy-1,3,5-triazine-6,2,4-triyldiimino)]hexakis[benzene-1,3-dicarboxylic acid] (5) were synthesized (Schemes,1 and 2) and characterized by means of 1H-NMR and FT-IR spectroscopy, elemental analysis, LC/MS analysis, AAS (atomic-absorption spectrum) analysis, thermal analyses, and magnetic-susceptibility measurements. The complexes can also be characterized as low-spin distorted-octahedral FeIII and CrIII complexes bridged by carboxylato moieties. [source] Structure-Based Design and Synthesis of the First Weak Non-Phosphate Inhibitors for IspF, an Enzyme in the Non-Mevalonate Pathway of Isoprenoid BiosynthesisHELVETICA CHIMICA ACTA, Issue 6 2007Corinne Baumgartner Abstract In this paper, we describe the structure-based design, synthesis, and biological evaluation of cytosine derivatives and analogues that inhibit IspF, an enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. This pathway is responsible for the biosynthesis of the C5 precursors to isoprenoids, isopentenyl diphosphate (IPP, 1) and dimethylallyl diphosphate (DMAPP, 2; Scheme,1). The non-mevalonate pathway is the sole source for 1 and 2 in the protozoan Plasmodium parasites. Since mammals exclusively utilize the alternative mevalonate pathway, the enzymes of the non-mevalonate pathway have been identified as attractive new drug targets in the fight against malaria. Based on computer modeling (cf. Figs.,2 and 3), new cytosine derivatives and analogues (Fig.,1) were selected as potential drug-like inhibitors of IspF protein, and synthesized (Schemes,2,5). Determination of the enzyme activity by 13C-NMR spectroscopy in the presence of the new ligands showed inhibitory activities for some of the prepared cytosine and pyridine-2,5-diamine derivatives in the upper micromolar range (IC50 values; Table). The data suggest that it is possible to inhibit IspF protein without binding to the polar diphosphate binding site and the side chain of Asp56,, which interacts with the ribose moiety of the substrate and substrate analogues. Furthermore, a new spacious sub-pocket was discovered which accommodates aromatic spacers between cytosine derivatives or analogues (binding to ,Pocket III') and rings that occupy the flexible hydrophobic region of ,Pocket II'. The proposed binding mode remains to be further validated by X-ray crystallography. [source] Asymmetric Lithiation of Boron Trifluoride-Activated Aminoferrocenes: An Experimental and Computational InvestigationADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 11-12 2010Costa Metallinos Abstract Tertiary aminoferrocenes complexed to boron trifluoride (BF3) are shown to undergo asymmetric lithiation with alkyllithiums in the presence of bulky chiral 1,2-diaminocyclohexane ligands. This reaction represents the first BF3 -activated asymmetric lithiation of a prochiral aromatic amine and the first such transformation to be mediated by a chiral diamine other than (,)-sparteine. The process provides rapid access to a broad range of enantiomerically enriched 2-substituted-1-aminoferrocenes, including derivatives with uncommon substitution patterns that are of interest in catalysis. The enantioselectivity of the process is high enough (87:13 to 91:9 er) to allow for isolation of single enantiomers of several products after simple recrystallization as either the free aminoferrocenes or their ammonium fluoroborate salts. Both antipodes of the planar chiral 2-substituted-1-aminoferrocene products are accessible, as confirmed by single crystal X-ray diffraction analysis of two compounds with opposite relative stereochemistry. Single-point calculation of thirty-two different transition states of the reaction at the M06-2X/6-311+g(2d,2p) level produced a computational model that correctly predicted both the sense and extent of chiral induction. Three factors appeared to play important roles in determining enantioinduction during lithiation of BF3 -complexed tertiary aminoferrocenes: (i) the maintenance of a highly organized eight-membered ring transition state; (ii) the existence of a strong Li,,,F contact which placed the chiral diamine ligand in close proximity to the ferrocene substrate; (iii) the orientation of the sterically demanding N -alkyl groups of the chiral diamine additives, either away or towards, the aminoferrocene and the alkyllithium. The model may serve as a predictive tool for the rational design of new ligands for this and related asymmetric lithiations. [source] Synthesis of new 4,5,6,7-tetrahydro-3H -imidazo[4,5- c]pyridine derivativesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 5 2003Miguel F. Braña The synthesis of new ligands for the H3 histamine receptor is described. These new compounds are spinacine derivatives obtained by alkylation or Michael reaction at C6 position. [source] Synthesis of 4,7,8a,9-tetrahydro-3H -diimidazo-[1,5- a:4,,5,- d]pyridine derivativesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 2 2002Miguel F. Braña The synthesis and evaluation of new ligands for the H3 receptor of histamine is described. These new compounds are diimidazopyridine derivatives readily prepared by a condensation reaction of spinacine and isocyanates. [source] Synthesis and characterization of 4,6-dichloroindole-based radioligands for imaging the glycine site of the NMDA ion channelJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 2 2002R. N. Waterhouse Abstract To provide effective PET or SPECT ligands for the glycine binding site of the NMDA ion channel, we have synthesized and characterized in vitro four substituted derivatives of the potent glycine site antagonist 3-[2-[(phenylamino)carbonyl]ethenyl]-4,6-dichloroindole-2-carboxylic acid (Ki=3.0 nM). These new ligands contain groups amenable to labeling with C-11 for PET, or I-123 for SPECT. In vitro analysis of these compounds revealed that placement of a methoxy group at either the ortho or para position of the phenylaminocarbonyl group significantly reduced receptor affinity (Ki=74.0±8.1 and 26.5±4.9 nM, respectively), as did placement of an iodine at the para position (Ki=60.4±8.2 nM). However, the meta -methoxy derivative (4b) maintained high affinity (Ki=4.8±0.9 nM) for the glycine site and was therefore labeled with carbon-11 by reacting the corresponding desmethyl derivative with [11C]methyl iodide. Radiochemical yields of 14±10% (EOS), and high specific activity (1.2±0.5 Ci/,mol (EOS, n=7)) were realized, and the product was prepared in a sterile saline solution suitable for in vivo use. Copyright © 2002 John Wiley & Sons, Ltd. [source] Solution structure of nociceptin peptidesJOURNAL OF PEPTIDE SCIENCE, Issue 9 2002Pietro Amodeo Abstract Peptides embedded in the sequence of pre-pro-nociceptin, i.e. nociceptin, nocistatin and orphanin FQ2, have shed light on the complexity of the mechanisms involving the peptide hormones related to pain and have opened up new perspectives for the clinical treatment of pain. The design of new ligands with high selectivity and bioavailability, in particular for ORL1, is important both for the elucidation and control of the physiological role of the receptor and for their therapeutic importance. The failure to obtain agonists and antagonists when using, for nociceptin, the same substitutions that are successful for opioids, and the conformational flexibility of them all, justify systematic efforts to study the solution conformation under conditions as close as possible to their natural environment. Structural studies of linear peptides in solution are hampered by their high flexibility. A direct structural study of the complex between a peptide and its receptor would overcome this difficulty, but such a study is not easy since opioid receptors are membrane proteins. Thus, conformational studies of lead peptides in solution are still important for drug design. This review deals with conformational studies of natural pre-nociceptin peptides in several solvents that mimic in part the different environments in which the peptides exert their action. None of the structural investigations yielded a completely reliable bioactive conformation, but the global conformation of the peptides in biomimetic environments can shed light on their interaction with receptors. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd. [source] A Tale of Two Targets: Differential RNA Selectivity of Nucleobase,Aminoglycoside ConjugatesCHEMBIOCHEM, Issue 10 2006Kenneth F. Blount Dr. Aminoglycoside antibiotics are RNA-binding polyamines that can bind with similar affinities to structurally diverse RNA targets. To design new semisynthetic aminoglycosides with improved target selectivity, it is important to understand the energetic and structural basis by which diverse RNA targets recognize similar ligands. It is also imperative to discover how novel aminoglycosides could be rationally designed to have enhanced selectivity for a given target. Two RNA drug targets, the prokaryotic ribosomal A-site and the HIV-1 TAR, provide an excellent model system in which to dissect the issue of target selectivity, in that they each have distinctive interactions with aminoglycosides. We report herein the design, synthesis, and binding activity of novel nucleobase,aminoglycoside conjugates that were engineered to be more selective for the A-site binding pocket. Contrary to the structural design, the conjugates bind the A-site more weakly than does the parent compound and bind the TAR more tightly than the parent compound. This result implies that the two RNA targets differ in their ability to adapt to structurally diverse ligands and thus have inherently different selectivities. This work emphasizes the importance of considering the inherent selectivity traits of the RNA target when engineering new ligands. [source] | |||||||||||||||||||||||||