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Chiral discrimination of 2-arylalkanoic acids by (1S,2R)-1-aminoindan-2-ol through the formation of a consistent columnar supramolecular hydrogen-bond network

Enantiopure cis-1-aminoindan-2-ol was selected as a basic resolving agent for racemic 2-arylalkanoic acids on the basis that its rigid cis-conformation would favor the formation of a supramolecular hydrogen-bonded column, in which chiral discrimination of the racemic carboxylate would occur. It was found that this amino alcohol possesses high resolving efficiency for a variety of racemic acids; also, X-ray crystallographic analyses of the diastereomeric salts showed that a columnar hydrogen-bond network is formed in both the less- and more-soluble diastereomeric salts, as we had expected. A detailed study on the stabilising interactions suggested that there are two that play an important role: (i) hydrogen bonding between the ammonium and hydroxy groups and the acid carboxylate, which determines the formation of the columnar network and (ii) CH…pi, which influences the herringbone packing of the aromatic groups, implying that it also plays some role in chiral discrimination.

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

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Asymmetric opening of the epoxide ring in cyclohexene oxide by thiophenol using homochiral phosphinamide catalysts

Enantiomerically pure phosphinamides containing a pendant hydroxyl group catalyse the Al(III)-promoted ring opening of the meso epoxide in cyclohexene oxide with thiophenol in up to 80% enantiomeric excess.

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

Archives for Chemistry Experiments of (1S,2R)-1-Amino-2,3-dihydro-1H-inden-2-ol

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Process for preparing an optically active phenylglycidyl acid derivative

The invention relates to a process for preparing an optically active trans-compound having formula (1), in which R represents a phenyl group, whether or not substituted, preferably p-methoxyphenyl, and A is derived from an optically active compound, in which an aldehyde having formula (2), in which R is as defined above, is, in the presence of a base, brought into contact with an optically active acetyl compound having formula (3), in which X represents a leaving group and in which A is derived from an amino alcohol, preferably a beta-amino alcohol having a rigid structure.Particularly good results were obtained when use was made of a compound having formula (3), in which A is derived from an amino indanol compound having formula (4), in which R 1 and R 2 represent a (hetero)alkyl or (hetero)aryl group, whether or not substituted, having 1-10 C atoms, or R 1 and R 2 constitute an aromatic or aliphatic ring together with the N atom to which they are bound, in particular in which R 1 and R 2 each independently of one another represent methyl, ethyl, isopropyl, n-propyl, n-butyl, allyl, benzyl or tosyl.

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

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Synthesis and antiviral activity of a series of HIV-1 protease inhibitors with functionality tethered to the P1 or P1’phenyl substituents: X-ray crystal structure assisted design

By tethering of a polar hydrophilic group to the P1 or P1′ substituent of a Phe-based hydroxyethylene isostere, the antiviral potency of a series of HIV protease inhibitors was improved. The optimum enhancement of anti-HIV activity was observed with the 4-morpholinylethoxy substituent. The substituent effect is consistent with a model derived from inhibitor docked in the crystal structure of the native enzyme. An X-ray crystal structure of the inhibited enzyme determined to 2.25 A verifies the modeling predictions.

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

Discovery of (1S,2R)-1-Amino-2,3-dihydro-1H-inden-2-ol

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Lipase-mediated resolution of trans-1-azidoindan-2-ol: A new route to optically pure cis-1-aminoindan-2-ol

Optically pure trans-1-azidoindan-2-ol has been prepared in both enantiomeric forms via lipase-mediated kinetic transesterification in organic solvent. A route to optically pure cis-1-aminoindan-2-ol has also been developed by using the optically pure trans-azidoalcohol thus obtained.

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

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Asymmetric conjugate addition of ketones to beta-nitrostyrenes by means of 1,2-amino-alcohol-derived prolinamides as bifunctional catalysts

Different L-prolinamides 21, prepared from L-proline and chiral beta-amino alcohols are active bifunctional catalysts for the direct nitro-Michael addition of ketones to beta-nitrostyrenes. In particular, catalyst 21e, prepared from L-proline and (1S,2R?)-cis-1-amino-2-indanol, exhibits the highest catalytic performance working in polar aprotic solvents such as NMP, especially in the presence of 20 mol-% of acid additives such as p-nitrobenzoic acid or under microwave heating. High syn diastereoselectivities (up to 94 % de) and good enantioselectivities (up to 80 % ee) are obtained at room temp. Moreover, catalyst 21e can be easily recovered and reused. ESI-MS studies are used to characterize the intermediates assumed for the catalytic cycle. The stereochemical control attending Michael addition reactions between ketones and nitrostyrenes catalyzed by prolinamide derivatives 21 has been investigated with computational density functional methods. Transition-state energies for the rate-limiting C-C bond-forming step are calculated. Analysis of these structures indicates that hydrogen bonding plays an important role in catalysis, and that the energy barrier for Re-face attack to form syn-(4S,5R) products is lower than that for Si-face attack leading to syn-(4R,5S) products. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

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

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Synthesis of a chiral fluorescence active probe and its application as an efficient catalyst in the asymmetric Friedel-Crafts alkylation of indole derivatives with nitroalkenes

Novel chiral Zn(ii) complexes were synthesized and these complexes showed fluorescence behaviour. These chiral Zn(ii) complexes were tested in the asymmetric Friedel-Crafts alkylation reaction of indole derivatives with nitroalkenes. In all the cases, the desired product was obtained with high yield (up to 93%) and good enantioselectivity (up to 78% ee) under the optimized reaction conditions. The effects of solvent, metallic salt and piperidine ratio on the fluorescence intensity of the catalyst and on the enantioselectivity of the desired products were discussed.

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

Final Thoughts on Chemistry for (1S,2R)-1-Amino-2,3-dihydro-1H-inden-2-ol

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Optimization of imidazole amide derivatives as cannabinoid-1 receptor antagonists for the treatment of obesity

Several imidazole-based cyclohexyl amides were identified as potent CB-1 antagonists, but they exhibited poor oral exposure in rodents. Incorporation of a hydroxyl moiety on the cyclohexyl ring provided a dramatic improvement in oral exposure, together with a ca. 10-fold decrease in potency. Further optimization provided the imidazole 2-hydroxy-cyclohexyl amide 45, which exhibited hCB-1 Ki = 3.7 nM, and caused significant appetite suppression and robust, dose-dependent reduction of body weight gain in industry-standard rat models.

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

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POLYMORPHIC FORM OF A TACHYKININ RECEPTOR ANTAGONIST

This invention is concerned with a novel polymorphic forms of the compound 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)4-( 5-(dimethyl-amino)methyl-1,2,3-triazol-4-yl)methyl-3-(S)-(4-fluorophenyl) morpholine hydrochloride which is a tachykinin receptor antagonist useful in the treatment or prevention of disorders of the central nervous system, inflammatory diseases, pain or migraine, asthma, and emesis. The instant polymorphic forms have advantages over the other known forms of 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)4-( 5-(dimethylamino)methyl-1, 2,3-triazol-4-yl)methyl-3-(S)-(4-fluorophenyl)morpholine hydrochloride in terms of thermodynamic stability and suitability for inclusion in pharmaceutical formulations.

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

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Method of producing cis-1-aminoindan-2-ol

1,2-di-substituted indan expressed by general formula (I) wherein X is a substituent which can be drawn out under an acidic condition to form a carbocation at 1-position of an indan skeleton, Y is a halogen atom, and X and Y can be in either cis- or trans-configuration forming either a racemic body or an optically active substance; or 1,2-di-substituted indan expressed by general formula (I’) wherein X is a substituent which can be drawn out under an acidic condition to form a carbocation at 1-position of an indan skeleton, and X and OH group can be in either cis- or trans-configuration forming either a racemic body or an optically-active substance; or cis-1,2-epoxyindan expressed by general formula (VI) wherein R is phenyl or a lower alkyl group, oxazoline ring is in cis-configuration forming either a racemic body or an optically active substance is reacted, under an acidic condition, with a nitrile expressed by general formula (II) wherein R is phenyl or a lower alkyl group to produce cis-1-aminoindan-2-ol expressed by general formula (V) wherein NH2 and OH groups are in cis-configuration forming either a racemic body or an optically-active substance. STR1

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