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An enantioselective total synthesis of the pseudopeptide microbial agent AI-77-B, which has shown potent antiulcerogenic properties, is described. The synthesis is convergent and involves the assembly of a dihydroisocoumarin fragment and a hydroxy amino acid. The dihydroisocoumarin derivative was synthesised by means of a Diels-Alder reaction between 1-methoxy-1,3-cyclohexadiene and an alkynyl ester derivative as the dienophile. The alkynyl ester was obtained stereoselectively by two different synthetic routes: (1) A stereoselective allylation of leucinal, and (2) a titanium enolate-mediated anti-aldol reaction with trichlorobutyraldehyde, a novel homopropargylaldehyde equivalent. The stereocentres of the hydroxy amino acid moiety were generated through a titanium enolate-mediated syn-aldol reaction, Curtius rearrangement, and application of Dondoni’s aldehyde homologation. Condensation of the dihydroisocoumarin and hydroxy amino acid moieties and subsequent removal of the protecting groups furnished optically active AI-77-B. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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A three-step degradation, including sequential ultrasonic extraction (UE), sequential thermal extraction (TE), and ruthenium ion-catalyzed oxidation (RICO), of Xianfeng lignite (XL) was performed to characterize the organonitrogen species (ONSs) in XL. More than 87.3% of organic matter in XL was converted into soluble portions through the degradation. The analysis with X-ray photoelectron spectrometer shows that pyrrolic, amino, and quaternary nitrogen species are the main nitrogen forms both in XL and its residue from UE, while nitroaromatics, chemisorbed N-oxides, and pyrrolic nitrogen are predominant in the residue from TE. A series of ONSs, including pyridines, quinolines, benzo[d]imidazoles, and arylamines, were identified in the extracts from TE of the UE residue according to GC/MS analysis. Among the ONSs, pyridines and quinolines are the most abundant. The ONSs could be released by thermally destroying noncovalent bonds, such as hydrogen bonds and aromatic pi – pi interactions, during TE of the UE residue. Most of ONSs released from RICO of the TE residue could be generated from the degradation of nitrogen-containing macromolecular aromatics in XL matrix (XLM). Nitrobenzenecarboxylic acids are the most abundant ONSs released from RICO of the TE residue and should be released by the degradation of macromolecular nitroaromatics in XLM.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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The aim of this study was to synthesize and evaluate a novel fluorine-18 labeled analogue of rasagiline (6) as a PET radioligand for monoamine oxidase B (MAO-B). The corresponding non-radioactive fluorine-19 ligand, (1S,2S)-2-fluoro-N-(prop-2-yn-1-yl)indan-1-amine (4), was characterized in in vitro assays. The precursor compound (3aS,8aR)-3-(prop-2-yn-1-yl)-3,3a,8,8a- tetrahydroindeno[1,2-d][1,2,3]oxathiazole 2,2-dioxide (3) and reference standard 4 were synthesized in multi-step syntheses. Recombinant human MAO-B and MAO-A enzyme preparations were used in order to determine IC50 values for compound 4 by use of an enzymatic assay employing kynuramine as substrate. Radiolabeling was accomplished by a two-step synthesis, compromising a nucleophilic substitution followed by hydrolysis of the sulphamidate group. Human whole hemisphere autoradiography (ARG) was performed with [ 18F]fluororasagiline. Blocking experiments with pirlindole (MAO-A), l-deprenyl and rasagiline (MAO-B) were conducted to demonstrate the specificity of the binding. A positron emission tomography (PET) study was carried out in a cynomolgus monkey where time activity curves for whole brain and regions with high and low MAO-B activity were recorded. Radiometabolites were measured in monkey plasma using gradient HPLC. Compound 4 inhibited MAO-B with an IC 50 of 27 nM and MAO-A with an IC50 of 2.3 muM. Radiolabeling of precursor 3 and subsequent hydrolysis of the protecting group towards (1S,2S)-2-[18F]fluoro-N-(prop-2-yn-1-yl)indan-1-amine (6) was successfully accomplished with an radiochemical yield of 40-70%, a radiochemical purity higher than 99% and a specific radioactivity higher than 200 GBq/mumol. ARG demonstrated selective binding for [18F] fluororasagiline (6) to MAO-B containing brain regions, for example, striatum. The initial uptake in the monkey brain was 250% SUV at 4 min post injection. The highest amounts of radioactivity were observed in the striatum and thalamus as expected whereas in the cortex and cerebellum lower levels were observed. Metabolite studies demonstrated 30% unchanged radioligand at 90 min post injection. Our investigations demonstrated that the new ligand [ 18F]fluororasagiline (6) binds specifically to MAO-B in vitro and has a MAO-B specific binding pattern in vivo. Thus, it could serve as a novel potential candidate for human PET studies.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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A series of chiral bifunctional squaramide multiple H-bond donor organocatalysts have been designed and synthesized by the rational assembly of chiral privileged scaffolds of indanol and cinchona alkaloids. In the presence of 1 mol % 1a, the asymmetric Michael addition reaction of 1,3-dicarbonyl compounds to nitroolefins proceeded to provide the product in high yields (up to 92%) and with good to high ee values (up to 96%). The additional H-bond in this squaramide system plays a crucial role in enhancing the enantioselectivity.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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To search for TNF-alpha (tumor necrosis factor alpha) converting enzyme (TACE) inhibitors, we designed a new class of macrocyclic hydroxamic acids by linking the P1 and P2? residues of acyclic anti-succinate-based hydroxamic acids. A variety of residues including amide, carbamate, alkyl, sulfonamido, Boc-amino, and amino were found to be suitable P1 P1-P2? linkers. With an N-methylamide at P3?, the 13-16-membered macrocycles prepared exhibited low micromolar activities in the inhibition of TNF-alpha release from LPS-stimulated human whole blood. Further elaboration in the P3?-P4? area using the cyclophane and cyclic carbamate templates led to the identification of a number of potent analogues with IC50 values of ?0.2 muM in whole blood assay (WBA). Although the P3? area can accommodate a broad array of structurally diversified functional groups including polar residues, hydrophobic residues, and amino and carboxylic acid moieties, in both the cyclophane series and the cyclic carbamate series, a glycine residue at P3? was identified as a critical structural component to achieve both good in vitro potency and good oral activity. With a glycine residue at P3?, an N-methylamide at P4? provided the best cyclophane analogue, SL422 (WBA IC50 = 0.22 muM, LPS-mouse ED50 = 15 mg/kg, po), whereas a morpholinylamide at P4? afforded the most potent and most orally active cyclic carbamate analogue, SP057 (WBAIC50 = 0.067 muM, LPS-mouse ED50 = 2.3 mg/kg, po). Further profiling for SL422 and SP057 showed that these macrocyclic compounds are potent TACE inhibitors, with Ki values of 12 and 4.2 nM in the porcine TACE assay, and are broad-spectrum MMP inhibitors. Pharmacokinetic studies in beagle dogs revealed that SL422 and SP057 are orally bioavailable, with oral bioavailabilities of 11% and 23%, respectively.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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Sewage sludge was pyrolysed in a quartz reactor at 350, 450, 550 and 950 C. The pyrolysis oils from the sewage sludge were characterized in detail by means of gas chromatography-mass spectrometry (GC-MS). Changes in the composition of the oils related to the process conditions were assessed by normalizing the areas of the peaks. It was demonstrated that, as the temperature of pyrolysis increased from 350 to 950 C, the concentration of mono-aromatic hydrocarbons in the oils also increased. Conversely, phenol and its alkyl derivatives showed a strong decrease in their concentration as temperature rose. Polycyclic aromatic hydrocarbons (PAHs) with two to three rings passed through a maximum at a pyrolysis temperature of 450 C. PAHs with 4-5 rings also presented a major increase as temperature increased up to 450 C, the concentration at 950 C being slightly higher than that at 450 C. Quantification of the main compounds showed that sewage sludge pyrolysis oils contain significant quantities of potentially high-value hydrocarbons such as mono-aromatic hydrocarbons and phenolic compounds. The oils also contain substantial concentrations of PAHs, even at the lowest temperature of 350 C. The pathway to PAH formation is believed to be via the Diels-Alder reaction and also via secondary reactions of oxygenated compounds such as phenols.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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New chiral amino-alcohols were enantioselectively synthesized using biotransformations as the key steps. They were used as ligand in the enantioselective borane reduction of acetophenone and of the corresponding anti oxime methyl ether.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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The glycolytic pathway has been considered a potential drug target against the parasitic protozoan species of Trypanosoma and Leishmania. We report the design and the synthesis of inhibitors targeted against Trypanosoma brucei phosphofructokinase (PFK) and Leishmania mexicana pyruvate kinase (PyK). Stepwise library synthesis and inhibitor design from a rational starting point identified furanose sugar amino amides as a novel class of inhibitors for both enzymes with IC50 values of 23 muM and 26 muM against PFK and PyK, respectively. Trypanocidal activity also showed potency in the low micromolar range and confirms these inhibitors as promising candidates for the development towards the design of anti-trypanosomal drugs.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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The catalyzed pathway has a lower Ea, but the net change in energy that results from the reaction is not affected by the presence of a catalyst. Computed Properties of C7H9N, If a proposed mechanism predicts the wrong experimental rate law, however, the mechanism must be incorrect.Welcome to check out more blogs about 108-47-4, in my other articles.

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The invention provides compounds of Formula I: 1where in W is 2These compounds may be in the form of pharmaceutical salts or compositions, racemic mixtures, or pure enantiomers thereof. The compounds of Formula I are useful to treat diseases or conditions in which alpha7 is known to be involved.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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A H2O-regulated chemoselective addition in oxa- and aza-Michael reactions for aminoalcohols and mixtures of structurally similar alcohols and amines was reported. The oxa-Michael reactions might be kinetically controlled, and the reactions to produce O-selective products were slowed by the addition of water. The electrophilicity of Michael acceptors and the steric hindrance of Michael donors also affect the ratios of O/N products. This method offers novel ideas over conventional metal-catalyzed or ligand-induced strategies.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis