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SULFAMOYL-ARYLAMIDES AND THE USE THEREOF AS MEDICAMENTS FOR THE TREATMENT OF HEPATITIS B

Inhibitors of HBV replication of Formula (I) including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein B, R1, R2 and R4 have the meaning as defined herein. The present invention also relates to pharmaceutical compositions containing these inhibitors and to their use, alone or in combination with other HBV inhibitors, in HBV therapy.

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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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Catalytic enantioselective alpha-tosyloxylation of ketones using iodoaryloxazoline catalysts: Insights on the stereoinduction process

A family of iodooxazoline catalysts was developed to promote the iodine(III)-mediated alpha-tosyloxylation of ketone derivatives. The alpha-tosyloxy ketones produced are polyvalent chiral synthons. Through this study, we have unearthed a unique mode of stereoinduction from the chiral oxazoline moiety, where the stereogenic center alpha to the oxazoline oxygen atom is significant. Computational chemistry was used to rationalize the stereoinduction process. The catalysts presented promote currently among the best levels of activity and selectivity for this transformation. Evaluation of the scope of the reaction is presented.

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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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Enantioselective synthesis of enantiopure beta-amino alcohols via kinetic resolution and asymmetric reductive amination by a robust transaminase from Mycobacterium vanbaalenii

Chiral beta-amino alcohols are very important chiral building block for preparing bioactive compounds for use in pharmaceutical and fine chemical industries. Synthesis of chiral beta-amino alcohols by transaminase is big challenging due to the strict substrate specificities and very low activity of the enzyme. In this work, a (R)-selective omega-transaminase (MVTA) from Mycobacterium vanbaalenii was employed as a biocatalyst for the first time for the synthesis of chiral beta-amino alcohol via kinetic resolution and asymmetric reductive amination. The enzyme was purified and characterized. Kinetic resolution of a set of racemic beta-amino alcohols including two cyclic beta-amino alcohols by MVTA was demonstrated, affording (R)-beta-amino alcohols, (1S, 2S)-trans-2-aminocyclopentanol and (1R, 2S)-cis-1-amino-2-indanols in >99% ee and 50?62% conversion. Asymmetric reductive amination of three alpha-hydroxy ketones (10?300 mM) by MVTA was conducted, (S)-beta-amino alcohols were obtained with >99% ee and 80?99% conversion. Preparation experiment for the reductive amination of 200 mM 2-hydroxyacetophenone by the resting cells of recombinant E. coli (MVTA) was proceeded smoothly and product (S)-2-amino-2-phenylethanol was obtained with 71% isolated yield, >99% ee and 68.6 g/L/d volumetric productivity. The current research proved that the MVTA is a robust enzyme for the preparation of chiral beta-amino alcohol with high volumetric productivity.

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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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In homogeneous catalysis, the catalyst is in the same phase as the reactant. The number of collisions between reactants and catalyst is at a maximum.In a patent, 126456-43-7, name is (1S,2R)-1-Amino-2,3-dihydro-1H-inden-2-ol, introducing its new discovery. Application In Synthesis of (1S,2R)-1-Amino-2,3-dihydro-1H-inden-2-ol

Design and synthesis of new potent C2-symmetric HIV-1 protease inhibitors. Use of L-mannaric acid as a peptidomimetic scaffold

A study on the use of derivatized carbohydrates as C2-symmetric HIV-1 protease inhibitors has been undertaken. L-Mannaric acid (6) was bis-O- benzylated at C-2 and C-5 and subsequently coupled with amino acids and amines to give C2-symmetric products based on C-terminal duplication. Potent HIV protease inhibitors, 28 K(i) = 0.4 nM and 43 K(i) = 0.2 nM, have been discovered, and two synthetic methodologies have been developed, one whereby these inhibitors can be prepared in just three chemical steps from commercially available materials. A remarkable increase in potency going from IC50 = 5000 nM (23) to IC50 = 15 nM (28) was observed upon exchanging – COOMe for -CONHMe in the inhibitor, resulting in the net addition of one hydrogen bond interaction between each of the two -NH- groups and the HIV protease backbone (Gly 48/148). The X-ray crystal structures of 43 and of 48 have been determined (Figures 5 and 6), revealing the binding mode of these inhibitors which will aid further design.

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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 enantioenriched azo compounds: Organocatalytic Michael addition of formaldehyde N-tert-butyl hydrazone to nitroalkenes

The unprecedented diaza-ene reaction of formaldehyde N-tert-butyl hydrazone with nitroalkenes can be efficiently catalyzed by an axially chiral bis-thiourea to afford the corresponding diazenes in good to excellent yields (60-96%) and moderate enantioselectivities, up to 84 : 16 er; additional transformation of diazenes into their tautomeric hydrazones proved to be operationally simple and high-yielding, affording bifunctional compounds which represent useful intermediates for the synthesis of enantioenriched beta-nitro-nitriles and derivatives thereof.

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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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Chiral squaramide as multiple H-bond donor organocatalysts for the asymmetric Michael addition of 1,3-dicarbonyl compounds to nitroolefins

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£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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Ultrasound-assisted synthesis of substituted 2-aminobenzimidazoles, 2-aminobenzoxazoles, and related heterocycles

A sonochemical method for the synthesis of 2-aminobenzimidazoles and 2-aminobenzoxazoles, as well as chiral aminooxazolines and a chiral substituted quinazolin-5-one is reported. Using the Ph3P?I2system in the presence of triethylamine as a desulfurization agent, monothioureas prepared in situ from the reaction of bis-nucleophiles with isothiocyanates underwent rapid cyclization to afford a variety of N-heterocyclic compounds in good to excellent yields under mild conditions.

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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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Kinetic resolution by copper-catalyzed azide-alkyne cycloaddition

The use of chiral pybox ligands imparts enantioselectivity to the Cu I-catalyzed azide-alkyne cycloaddition reaction, in the form of kinetic resolution of alpha-chiral azides and desymmetrization of gem-diazides. While levels of selectivity are modest, the results show unequivocally that the process benefits from ligand-accelerated catalysis.

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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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Design, asymmetric synthesis, and evaluation of pseudosymmetric sulfoximine inhibitors against HIV-1 protease

The HIV-1 protease is a validated drug target for the design of antiretroviral drugs to combat AIDS. We previously established the sulfoximine functionality as a valid transition state mimetic (TSM) in the HIV-1 protease inhibitors (PI) design and have identified a lead pseudosymmetric compound with nanomolar enzymatic inhibitory activity. Here, we report the asymmetric synthesis of this compound and its application in the synthesis of sulfoximine-based peptidomimetic HIV-1 protease inhibitors. Molecular modeling revealed the potential mode of binding of the sulfoximine inhibitor as a TSM. The predicted absolute binding free energies suggested similar inhibitory effect as observed in our enzymatic inhibitory studies.

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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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General and Stereoselective Method for the Synthesis of Sterically Congested and Structurally Diverse P-Stereogenic Secondary Phosphine Oxides

A general and efficient method for the synthesis of bulky and structurally diverse P-stereogenic chiral secondary phosphine oxides (SPOs) by using readily available chiral amino alcohol templates is described. These chiral SPOs could be used as chiral building blocks for the synthesis of difficult-to-access bulky P-stereogenic phosphine compounds or ligands for organic catalysis.

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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