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A series of HIV protease inhibitor based on the allophenylnorstatine structure with various P2? moieties were synthesized. Among these analogues, we discovered that a small allyl group would maintain potent enzyme inhibitory activity compared to the o-methylbenzyl moiety in clinical candidate 1 (KNI-764, also known as JE-2147, AG-1776, or SM-319777). Introduction of an anilinic amino group to 2 (KNI-727) improved water-solubility and anti-HIV-1 activity. X-ray crystallographic analysis of 13k (KNI-1689) with a beta-methallyl group at P2? position revealed hydrophobic interactions with Ala28, Ile84, and Ile50? similar to that of 1. The presence of an additional methyl group on the allyl group in compound 13k significantly increased anti-HIV activity over 1 while providing a rational drug design for structural minimization and improving membrane permeability.

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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 C2-symmetric compounds with a mannitol-based scaffold has been investigated, both theoretically and experimentally, as Plm II inhibitors. Four different stereoisomers with either benzyloxy or allyloxy P1/P1? side chains were studied. Computational ranking of the binding affinities of the eight compounds was carried out using the linear interaction energy (LIE) method relying on a complex previously determined by crystallography. Within both series of isomers the theoretical binding energies were in agreement with the enzymatic measurements, illustrating the power of the LIE method for the prediction of ligand affinities prior to synthesis. The structural models of the enzyme-inhibitor complexes obtained from the MD simulations provided a basis for interpretation of further structure-activity relationships. Hence, the affinity of a structurally similar ligand, but with a different P2/P2? substituent was examined using the same procedure. The predicted improvement in binding constant agreed well with experimental results.

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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 novel study on the influence of external Bronsted acids on thiourea catalysts in the asymmetric Friedel-Crafts alkylation of indoles with nitroalkenes is reported. The final 3-substituted indole derivatives were synthesized with better results because of cooperative effects between the chiral thiourea and a Bronsted acid additive (1a·HA). The effects of diverse catalysts, different acid additives, solvents, and temperatures in the reaction were also explored. The high reactivity and selectivity of the reaction is presumptively attributed to an appropriate assembly between the Bronsted acid and the thiourea structure, affording a more acidic and rigid catalytic complex. Copyright

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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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Practical chiroptical sensing with a small group of commercially available aromatic aldehydes is demonstrated. Schiff base formation between the electron-deficient 2,4-dinitrobenzaldehyde probe and either primary amines, diamines, or amino alcohols proceeds smoothly in chloroform at room temperature and is completed in the presence of molecular sieves within 2.5 hours. The substrate binding coincides with a distinct circular dichroism signal induction at approximately 330 nm, which can be correlated to the absolute configuration and enantiomeric composition of the analyte. The usefulness of this sensing method is highlighted with the successful sensing of 18 aliphatic and aromatic amines and amino alcohols and five examples showing quantitative %ee determination with good accuracy.

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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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This invention relates to novel compounds suitable for labelling by 18F and the corresponding 18F labelled compounds themselves, 19F-fluorinated analogues thereof and their use as reference standards, methods of preparing such compounds, compositions comprising such compounds, kits comprising such compounds or compositions and uses of such compounds, compositions or kits for diagnostic imaging by Positron Emission Tomography (PET).

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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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An efficient asymmetric desymmetrization of meso-epoxides with anilines catalysed by a series of simple and environmentally benign in situ generated Fe(iii) complexes based on chiral tridentate ligands L1-L7 with achiral and chiral linkers (methylene, piperazine, R/S BINOL and diethyl tartrate) was carried out at rt. The in situ generated iron metal complex based on ligand L5a emerged as improved (low catalyst loading) catalyst for asymmetric desymmetrization of meso-epoxides with anilines giving high enantioselectivity (up to 99%) and high yield (95%) of enantiopure beta-amino alcohols in 14 h. While excellent results for ARO of cyclic as well as aliphatic epoxides with anilines was achieved with in situ generated complex from the ligand L4h and Fe(iii) chloride, the catalyst was recoverable and recyclable (five times) with retention of its performance.

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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 biphosphines, e.g., STR1 are useful as key components in catalysts for asymmetric reactions, providing desirably high enantiomeric excess (ee).

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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 reaction of cyclopentadiene with various bidentate dienophiles in the presence of 4-10 mol% of copper(II)-bis(oxazoline) complexes afforded excellent endo/exo selectivity as well as endo enantioselectivity (95-99% ee) and isolated yields. On the other hand, Diels-Alder reaction with Mg(II)- complexes afforded a modest (61% ee) reversal in 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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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:
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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Investigations into the mechanistic aspects of the stereospecific interaction of the four optical isomers of aminoindanol on a silica based crown ether column were performed. The nature and concentration of the mobile phase’s counteranion affected the hydrophobic interaction but had little effect on the inclusion interaction. Minimal changes in the separation factor of the enantiomers were observed in the pH range of 1-5.2, but a minimum in the capacity factor was observed at pH 3.75. Van’t Hoff plots indicated a high entropy and a positive enthalpy at pH 5.2, while a lower entropy and a negative enthalpy were observed at and below pH 3.75. Hill plots indicated that there were more active binding sites at pH 3.0 as compared to pH 1.0 and that the binding ratio of aminoindanol to active sites was also greater. Apparently at higher pH values, as the silica becomes deprotonated, there is an additional electrostatic interaction between the protonated aminoindanol and the deprotonated silica sites.

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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