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The large-scale production of enantiopure compounds in a cost-effective and environmentally friendly manner remains one of the major challenges of modern-day chemistry. The resolution of racemates through enantioselective liquid?liquid extraction was developed as a suitable solution but has remained largely underused, owing to a lack of highly efficient and robust chiral hosts to mediate the process. This paucity of hosts can in part be attributed to a poor understanding of the underlying principles behind these processes hindering the design of more efficient selectors. A previously untested class of hosts, VAPOL and VANOL derived phosphoric acids, has been studied in depth for the efficient enantioselective liquid?liquid extraction of 1,2-amino alcohols. A systematic investigation of extraction parameters was conducted, revealing many key interactions and DFT calculations illustrate the binding modes for the 1:1 complexes that are involved in chiral recognition. The resulting, now-optimized, procedures are highly robust and easy to implement. They are also easily scalable, as demonstrated by U-tube experiments.

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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 highly stereoselective asymmetric 6pi-azaelectrocyclization was achieved as a general synthetic method based on the reaction between the (E)-3-carbonyl-2,4,6-trienal compounds and the (-)-7-alkyl-cis-l-amino-2-indanol derivatives which are effective chiral amines. The 7-alkyl-substituted 2-indanol moiety of the cyclized products was efficiently removed by the novel manganese dioxide oxidation under remarkably mild conditions, and the method was successfully applied to the formal synthesis of optically active 20-epiuleine.

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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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Provided is a production method of an optically active dihydrobenzofuran derivative. A production method of an optically active form of a compound represented by the formula: wherein each symbol is as defined in the specification, or a salt thereof and the like.

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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

Our Top Choice Compound: C9H11NO

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This invention provides a convenient method for converting imines and other electrophiles into heterocyclic ring systems. The process does not require the use of metallic reagents, and is catalyzed by an organic heterocyclic carbene catalyst. Accordingly, it produces the desired compounds without the concomitant production of a large volume of metallic waste. Chiral heterocyclic carbene catalysts of the invention and methods of using these catalysts produce chiral heterocycles in high enantiomeric and diastereomeric 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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[PROBLEM TO BE SOLVED]: To provide a method for producing pyridine bases in good yield using aliphatic aldehyde, aliphatic ketone or those mixture as a raw material[SOLUTION]: The method for producing pyridine bases is characterized by reacting aliphatic aldehyde, aliphatic ketone or those mixture with ammonia in vapour phase in the presence of the zeolite catalyst that contains titanium and/or cobalt, boron, and silicon as constituent elements.In addition, it is desirable that the zeolite catalyst contains at least a kind of ion and/or compound selected from 12th – 14th element.For example, acetaldehyde etc. are enumerated as a aliphatic aldehyde, aliphatic ketone or those mixture

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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

Our Top Choice Compound: C9H11NO

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Anti-succinate hydroxamates with cyclic P1 motifs were synthesized as aggrecanase inhibitors. The N-methanesulfonyl piperidine 23 and the N-trifluoroacetyl azetidine 26 were the most potent aggrecanase inhibitors both having an IC50=3 nM while maintaining >100-fold selectivity over MMP-1, -2, and -9. The cyclic moieties were also capable of altering in vivo metabolism, hence delivering low clearance compounds in both rat and dog studies as shown for compound 14.

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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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One ring to bring them all: 4,5-Spirocycles derived from 3-oxetanone and beta-heteroatom-substituted amino compounds undergo a Lewis acid mediated reaction cascade to form saturated nitrogen heterocycles. The unique reactivity of 3-oxetanone facilitates access to biologically important morpholines, piperazines, and thiomorpholines with an otherwise difficult-to-access substitution pattern from readily available starting materials. 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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The 13C-NMR spectrum of {[NON]Zr(13CH3)(S)}+ (S=bromobenzene-d5) after addition of one equivalent of 1-hexene reveals resonances at 30.8 ppm for the terminal 13CH3 group in the first insertion product, at 24.0 ppm for the terminal 13CH3 group in the second insertion product and near 20 ppm for the terminal 13CH3 group in higher insertion products. The latter are consistent with ‘insertion’ of the 1-hexene into the Zr-CH3 bond in a 1,2 manner. Addition of ten equivalents of 1-nonene to {[NON]Zr(CH3)(S)}+ followed by one equivalent of 13CH2=CHC7H15 led to a 13C-NMR spectrum consistent with formation of {[NON]Zr[13CH2CH(C7H 15)(Polymer)](S)}+, which confirms that 1-nonene ‘inserts’ into the Zr-C bond primarily in a 1,2 fashion. A discussion as to why beta elimination is relatively slow in {[NON]Zr(R)(S)}+ systems that have been examined so far focuses on reversible addition of a terminal olefin only to the CNN face of the pseudo-tetrahedral cation, {[NON]Zr(R)}+, to yield a trigonal bipyramidal transition state. After the equatorial alkyl group migrates to the substituted carbon of the incoming olefin, the new bulky alkyl in {[NON]Zr(CH2CHPR?)}+ cannot ‘back up’ toward the two t-butyl groups in preparation for beta elimination relative to the rate at which {[NON]Zr(CH2CHPR?)}+ reacts with either base or more olefin.

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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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Cancer is the leading cause of death among men and women under age 85. Every year, millions of individuals are diagnosed with cancer. But finding new drugs is a complex, expensive, and very time-consuming task. Over the past decade, the cancer research community has begun to address the in silico modeling approaches, such as Quantitative Structure-Activity Relationships (QSAR), as an important alternative tool for targeting potential anticancer drugs. With the compilation of a large dataset of nucleosides synthesized in our laboratories, or elsewhere, and tested in a single cytotoxic assay under the same experimental conditions, we recognized a unique opportunity to attempt to build predictive QSAR models. Early efforts with 2D classification models built from part of this dataset were very encouraging. Here we report a further detailed evaluation of classification models to flag potential anticancer activities derived from a variety of 3D molecular representations. A quantitative 3D-model model that discriminates anticancer compounds from the inactive ones was attained, which allowed the correct classification of 82% of compounds in such a large and diverse dataset, with only 5% of false inactives and 11% of false actives. The model developed here was then used to select and design a new series of nucleosides, by classifying beforehand them as active/inactive anticancer compounds. From the compounds so designed, 22 were synthesized and evaluated for their inhibitory effects on the proliferation of murine leukemia cells (L1210/0), of which 86% were well-classified as active or inactive, and only two were false actives, corroborating the good predictive ability of the present discriminant model. The results of this study thus provide a valuable tool for the design of novel potent anticancer nucleoside analogues.

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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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Crossing N-bridges! A ruthenium/N-heterocyclic carbene (NHC) complex serves as the catalyst for the high-yielding and completely regioselective and asymmetric hydrogenation of substituted indolizines and 1,2,3-triazolo-[1,5-a] pyridines. This method should provide ready access to bicyclic products bearing an N-bridgehead, a motif appearing in 25-30 % of all naturally occurring alkaloids. 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