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Self-assembly of a stereodynamic phosphine ligand, Pd(II), and a chiral amine, amino alcohol, or amino acid generates characteristic UV and CD signals that can be used for quantitative stereochemical analysis of the bound substrate. A robust mix-and-measure chiroptical sensing protocol has been developed and used to determine the absolute configuration, ee, and yield of an amine produced by Ir-catalyzed asymmetric hydrogenation of an iminium salt. The analysis requires only 1 mg of the crude reaction mixture and minimizes cost, labor, time, and waste.

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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 improved process using chiral hydrogenation is described for the synthesis in high yields of a 4-protected-(S)-piperazine-2-tert-butylcarboxamide, an intermediate for an HIV protease inhibitor.

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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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(Equation presented) A practical synthesis of sultams was developed via intramolecular sulfonamide dianion alkylation. This method has been applied toward the synthesis of chiral sultams, which are synthetically valuable as chiral auxiliaries.

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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 synthesis of (1S,2R)-1-amino-2-indanol (1), a key component of an HIV protease inhibitor, was accomplished through (R)-2-hydroxy-1-indanone ((R)- 3), which was prepared by an intramolecular Friedel-Crafts acylation of (R)2- acetoxy-3-phenylpropanoic acid readily available from D-(R)-phenylalanine. Alternatively, (R)-3 was obtained by an enzymatic resolution of (±)-2- acetoxy-1-indanone. Ketone (R)-3 was convened into 1 through an oxime formation and diastereoselective hydrogenation.

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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 present disclosure provides processes for the preparation of a compound of formula I: which is useful as an antiviral agent. The disclosure also provides compounds that are synthetic intermediates to compounds of formula I.

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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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With the aim of developing small molecular non-peptide beta-secretase (BACE) inhibitors, Leu*Ala hydroxyethylene (HE) was investigated as a scaffold to design and synthesize a series of compounds. Taking advantage of efficient combinatorial synthesis approaches and molecular modeling, extensive structure-activity relationship (SAR) studies were carried out on the N- and C-terminal residues of the Leu*Ala HE scaffold. Isobutyl amine was found to be an optimal C-cap, and suitable hydroxylalkylamines at the 3-position and nitro or methyl(methylsulfonyl)amine at the 5-position of isophthalamide as the N-terminus could form additional hydrogen bonds with BACE active sites and help improve potency. Many new potent non-peptide BACE inhibitors were identified in this study. Among them, compounds 37 and 44 exhibited excellent enzyme-inhibiting potency, comparable to that of OM99-2, and obvious inhibitory effects in cell-based assay with low molecular weights (<600). Because enzymes can increase reaction rates by enormous factors and tend to be very specific, they are the focus of active research. Each step is an elementary reaction. In my other articles, you can also check out more blogs about 126456-43-7 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 organocatalytic Friedel-Crafts alkylation of indoles with alpha,beta-unsaturated ketones was found to be efficiently accelerated under high-pressure conditions with a low loading of chiral primary amine salts with good yield and enantioselectivity up to 90%. This approach also allows, for the first time, selected indole derivatives containing quaternary stereogenic centers to be obtained from prochiral beta,beta-disubstituted enones with an enantioselectivity up to 80%.

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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 synthesis of novel, potent, diol-based HIV-1 protease inhibitors, having phenethyl groups (-CH2CH2Ph) in P1/P1? position is described. An intermolecular pinacol homocoupling of (2S)-2-benzyloxymethyl-4-phenylbutanal 16 was the key step in the synthesis. From this reaction sequence four carba analogues, compounds 8a, 8b, 9a, and 9b, were prepared, having the inverted configuration of one or both of the stereogenic centers carrying the diol hydroxyls as compared to the parent series represented by inhibitors 6 and 7. Inhibitor 8b was found to be a potent inhibitor of HIV-1 protease (PR), showing excellent antiviral activity in the cell-based assay and in the presence of 40% human serum. The absolute stereochemistry of the central diol of the potent inhibitor (8b) was determined from the X-ray crystallographic structure of its complex with HIV-1 PR.

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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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Sequential treatment of 2-C6H4Br(CHO) with LiC?CR1(R1=SiMe3, tBu), nBuLi, CuBr?SMe2and HC?CCHClR2[R2=Ph, 4-CF3Ph, 3-CNPh, 4-(MeO2C)Ph] at ?50 C leads to formation of an intermediate carbanion (Z)-1,2-C6H4{CA(=O)C?CBR1}{CH=CH(CH?)R2} (4). Low temperatures (?50 C) favour attack at CBleading to kinetic formation of 6,8-bicycles containing non-classical C-carbanion enolates (5). Higher temperatures (?10 C to ambient) and electron-deficient R2favour retro sigma-bond C?C cleavage regenerating 4, which subsequently closes on CAproviding 6,6-bicyclic alkoxides (6). Computational modelling (CBS-QB3) indicated that both pathways are viable and of similar energies. Reaction of 6 with H+gave 1,2-dihydronaphthalen-1-ols, or under dehydrating conditions, 2-aryl-1-alkynylnaphthlenes. Enolates 5 react in situ with: H2O, D2O, I2, allylbromide, S2Me2, CO2and lead to the expected C-E derivatives (E=H, D, I, allyl, SMe, CO2H) in 49?64 % yield directly from intermediate 5. The parents (E=H; R1=SiMe3, tBu; R2=Ph) are versatile starting materials for NaBH4and Grignard C=O additions, desilylation (when R1=SiMe) and oxime formation. The latter allows formation of 6,9-bicyclics via Beckmann rearrangement. The 6,8-ring iodides are suitable Suzuki precursors for Pd-catalysed C?C coupling (81?87 %), whereas the carboxylic acids readily form amides under T3P conditions (71?95 %).

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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 new generation of HIV-1 protease inhibitors encompassing a tertiary-alcohol-based transition-state mimic has been developed. By elongation of the core structure of recently reported inhibitors with two carbon atoms and by varying the P1? group of the compounds, efficient inhibitors were obtained with Ki down to 2.3 nM and EC50 down to 0.17 muM. Two inhibitor-enzyme X-ray structures are reported.

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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