5962-96-9Relevant academic research and scientific papers
SUBSTITUTED THIAZOLE COMPOUNDS
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Page/Page column 19, (2014/06/24)
The invention is concerned with the compounds of formula (I) and pharmaceutically acceptable salts thereof. In addition, the present invention relates to methods of manufacturing and using the compounds of formula (I) as well as pharmaceutical compositions containing such compounds. The compounds of formula (I) are LMP7 inhibitors and may be useful in treating associated inflammatory diseases and disorders such as, for example, rheumatoid arthritis, lupus and irritable bowel disease.
Asymmetric hydrogenation of maleic acid diesters and anhydrides
Bernasconi, Maurizio,Mueller, Marc-Andre,Pfaltz, Andreas
supporting information, p. 5385 - 5388 (2014/06/09)
Asymmetric hydrogenation of maleic and fumaric acid derivatives with iridium catalysts based on N,P ligands provides an efficient route to chiral enantioenriched succinates. A new catalyst derived from a 2,6-difluorophenyl- substituted pyridine-phosphinite ligand was developed and enables the conversion of a wide range of 2-alkyl and 2-arylmaleic acid diesters into the corresponding succinates in high enantiomeric purity. Mixtures of cis/trans substrates can be hydrogenated in an enantioconvergent fashion with high enantioselectivity, and further enhances the scope of this transformation. The products are valuable chiral building blocks with a structural motif found in many bioactive compounds, such as metalloproteinase inhibitors. An attractive enantioselective route to 2-alkyl- and 2-aryl-substituted succinic acid derivatives is opened up by the asymmetric hydrogenation of maleic and fumaric acid derivatives, using the new catalyst [Ir(cod)L]BArF, derived from a 2,6-difluorophenyl-substituted pyridine-phosphinite ligand. The products are valuable chiral building blocks having a structural motif found in many bioactive compounds. cod=1,5-cyclooctadiene.
Succinic anhydrides from epoxides
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Page/Page column 24; 25; 26, (2013/07/25)
Catalysts and methods for the double carbonylation of epoxides are disclosed. Each epoxide molecule reacts with two molecules of carbon monoxide to produce a succinic anhydride. The reaction is facilitated by catalysts combining a Lewis acidic species with a transition metal carbonyl complex. The double carbonylation is achieved in single process by using reaction conditions under which both carbonylation reactions occur without the necessity of isolating or purifying the product of the first carbonylation.
Catalytic double carbonylation of epoxides to succinic anhydrides: Catalyst discovery, reaction scope, and mechanism
Rowley, John M.,Lobkovsky, Emil B.,Coates, Geoffrey W.
, p. 4948 - 4960 (2008/02/03)
The first catalytic method for the efficient conversion of epoxides to succinic anhydrides via one-pot double carbonylation is reported. This reaction occurs in two stages: first, the epoxide is carbonylated to a β-lactone, and then the β-lactone is subsequently carbonylated to a succinic anhydride. This reaction is made possible by the bimetallic catalyst [(CITPP)Al(THF)2]+[Co(CO)4]- (1; CITPP = meso-tetra(4-chlorophenyl)porphyrinato; THF = tetrahydrofuran), which is highly active and selective for both epoxide and lactone carbonylation, and by the identification of a solvent that facilitates both stages. The catalysis is compatible with substituted epoxides having aliphatic, aromatic, alkene, ether, ester, alcohol, nitrile, and amide functional groups. Disubstituted and enantiomerically pure anhydrides are synthesized from epoxides with excellent retention of stereochemical purity. The mechanism of epoxide double carbonylation with 1 was investigated by in situ IR spectroscopy, which reveals that the two carbonylation stages are sequential and non-overlapping, such that epoxide carbonylation goes to completion before any of the intermediate β-lactone is consumed. The rates of both epoxide and lactone carbonylation are independent of carbon monoxide pressure and are first-order in the concentration of 1. The stages differ in that the rate of epoxide carbonylation is independent of substrate concentration and first-order in donor solvent, whereas the rate of lactone carbonylation is first-order in lactone and inversely dependent on the concentration of donor solvent. The opposite solvent effects and substrate order for these two stages are rationalized in terms of different resting states and rate-determining steps for each carbonylation reaction.
Synthesis, nicotinic acetylcholine receptor binding, antinociceptive and seizure properties of methyllycaconitine analogs
Ivy Carroll,Ma, Wei,Navarro, Hernan A.,Abraham, Philip,Wolckenhauer, Scott A.,Damaj,Martin, Billy R.
, p. 678 - 685 (2007/10/03)
A series of methyllycaconitine (1a, MLA) analogs was synthesized where the (S)-2-methylsuccinimidobenzoyl group in MLA was replaced with a (R)-2-methyl, 2,2-dimethyl-, 2,3-dimethyl, 2-phenyl-, and 2-cyclohexylsuccinimidobenzoyl (1b-f) group. The analogs 1b-f were evaluated for their inhibition of [125I]iodo-MLA binding at rat brain α7 nicotinic acetylcholine receptors (nAChR). In order to determine selectivity, MLA and the analogs 1b-f were evaluated for inhibition of binding to rat brain α,β nAChR using [3H]epibatidine. At the α7 nAChR, MLA showed a Ki value of 0.87 nM, analogs 1b-e possessed Ki values of 1.67-2.16 nM, and 1f showed a Ki value of 26.8 nM. Surprisingly, the analog 1e containing the large phenyl substituent (Ki = 1.67 nM) possessed the highest affinity. None of the compounds possessed appreciable affinity for α,β nAChRs. MLA antagonized nicotine-induced seizures with an AD50 = 2 mg/kg. None of the MLA analogs were as potent as MLA in this assay. MLA and all of the MLA analogs, with the exception of 1b, antagonized nicotine's antinociceptive effects in the tail-flick assay. Compound 1c (Ki = 1.78 nM at α7 nAChR) with an AD50 value of 1.8 mg/kg was 6.7 times more potent than MLA (AD50 = 12 mg/kg) in antagonizing nicotine's antinociceptive effects but was 5-fold less potent than MLA in blocking nicotine-induced seizures. Since MLA has been reported to show neuroprotection against β-amyloid1-42, these new analogs which have high α7 nAChR affinity and good selectivity relative to α,β nAChRs will be useful biological tools for studying the effects of α7 nAChR antagonist and neuroprotection.
Stereoselectivity of the Transfer of Hydrogen Atoms to Cyclic Alkyl Radicals
Metzger, Juergen O.,Schwarzkopf, Kay,Saak, Wolfgang,Pohl, Siegfried
, p. 1069 - 1074 (2007/10/02)
The addition of cyclohexane to alkylmaleic anhydrides 1a-f via cyclic radicals 2a-f gave a mixture of (Z)- and (E)-2,3-dialkylsuccinic anhydrides 3a-f.The stereoselectivity of the hydrogen transfer from cyclohexane to radicals 2a-d was measured in the temperature range of 200-260 deg C, and the relative activation parameters of the formation of (Z)- and (E)-3 were determined.The stereoselectivity of the hydrogen transfer from cyclohexylmercuric hydride at 25 deg C was measured as well.The results are rationalized assuming steric interactions in the transition state of H donor and β substituent and of α and β substituent, respectively.An X-ray structure analysis of the highly strained addition product (Z)-3d was performed. - Key Words: Free-radical additions / Alkyl radicals / Stereoselectivity / Hydrogen transfer
13C Chemical Shift Non-Equivalence in Methylene Carbons of Monosubstituted Cyclohexanes
Ito, Hiroshi,Renaldo, Alfred F.,Johnson, Robert D.,Ueda, Mitsuru
, p. 273 - 276 (2007/10/02)
Monosubstituted cyclohexanes were synthesized by addition of a cyclohexyl radical to olefins bearing different substituents at the α-position.Six distinct methylene 13C resonances were observed, indicating that the methylene carbons located at the 2 and 6 positions and at 3 and 5 positions are not magnetically equivalent.This magnetic non-equivalence (anisochronism) observed in the monosubstituted cyclohexanes is due to the introduction of an asymmetric center β to the prochiral C-1 ring carbon atom. KEY WORDS Anisochronism Magnetic non-equivalence Cyclohexyl adducts Mercury method
Radical Chain Reactions with Maleic Anhydrides - Contrathermodynamic Stereoselectivity
Giese, Bernd,Kretzschmar, Gerhard
, p. 3175 - 3182 (2007/10/02)
The reactions of cyclohexylmercuric chloride with NaBH4 and alkenes 1a-g yield 60-84percent of products 3, 4 and 6 in a radical chain process (table 1).Caused by steric effects of substituents Z at least 97percent of the radical attack occurs at the unsubstituted carbon atom of maleic anhydrides 1c-g.Only fluoromaleic anhydride 1b is attacked by cyclohexyl radicals predominantly at the substituted carbon atom, because fluorine is a tiny, electron releasing substituent.Radicals 2 are trapped predominantly from the anti-direction by the H-donor (figure 1), yielding cis-compounds 3as main products.This "contrathermodynamic" stereoselectivity ranges between 2.3 and 19 (table 1).
Radical Addition to Cyclic Derivatives of Maleic Acid
Giese, Bernd,Kretzschmar, Gerhard
, p. 2012 - 2014 (2007/10/02)
Reactions of cyclohexylmercury acetate (I) with NaBH4 in the presence of cyclic alkenes 4 yield the products 5 in high yields (Tab. 1).The main step of the reaction sequence is the addition of a cyclohexyl radical to the alkene 4.The rate of the addition
Ashless additives for lubricating compositions
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, (2008/06/13)
Superior ashless additives for lubricants are prepared by a process comprising first introducing a petroleum sulfonic acid and a polyamine to a reaction zone and subsequently introducing a cyclic anhydride of a dicarboxylic acid into the reaction zone. In another embodiment, the solids content of the additives is reduced to acceptable levels by removal of free SO2 from the petroleum sulfonic acid prior to preparing the additive. Lubricating oil compositions containing these ashless additives are also provided.
