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The central effects of L-proline, D-proline and trans-4-hydroxy-L-proline were investigated by using the acute stressful model with neonatal chicks in Experiment 1. Sedative and hypnotic effects were induced by all compounds, while plasma corticosterone release under isolation stress was only attenuated by L-proline. To clarify the mechanism by which L-proline and D-proline induce sedative and hypnotic effects, the contribution of the strychnine-sensitive glycine receptor (glycine receptor) and N-methyl-D-aspartate glutamate receptor (NMDA receptor) were further investigated. In Experiments 2-3, the glycine receptor antagonist strychnine was co-injected intracerebroventricular (i.c.v.) with L-proline or D-proline. The suppression of isolation-induced stress behavior by D-proline was attenuated by strychnine. However, the suppression of stress behavior by L-proline was not attenuated. In Experiment 4, the NMDA receptor antagonist (+)-MK-801 was co-injected i.c.v. with L-proline. The suppression of stress behavior by L-proline was attenuated by (+)-MK-801. These results indicate that L-proline and D-proline differentially induce sedative and hypnotic effects through NMDA and glycine receptors, respectively.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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3-Carboxy-3,4-dehydropyrrolidine was found to bind with affinity equal to that of glycine in a [3H]strychnine binding assay. Simple substitution of the 1-, 2-, 4-, or 5-position resulted in marked loss of affinity. A decline in affinity was also found upon enlargement, contraction, or saturation of the 5-membered ring. However, beta-proline and azetidine-3-carboxylic acid retained significant binding affinity. Despite its good affinity in [3H]strychnine binding, 3-carboxy-3,4-dehydropyrrolidine showed only weak agonist activity in intracellular recordings of cultured murine spinal cord neurons. This apparent lack of correlation between binding and functional results is discussed in light of the current models of the strychnine- sensitive glycine receptor.

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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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The beta-diketonate-based achiral polymer P-1 could be synthesized by the polymerization of 3,7-dibromo-2,8-dimethoxy-5,5-dioctyl-5H-dibenzo[b,d]silole (M1) with (Z)-1,3-bis(4-ethynylphenyl)-3-hydroxyprop-en-1-one (M2) via typical Sonogashira coupling reaction. The beta-diketonate unit in the main chain backbone of P-1 can further coordinate with Eu(TTA)x [TTA-=4,4,4-trifluoro-1-(thiophen-2-yl)butane-1,3-dionate anion, X=1, 2, 3] to afford corresponding Eu(III)-containing polymer complexes. The resulting achiral polymer complex P-2 (X=2) can exhibit strong circular dichroism (CD) response toward both N-Boc-l and d-proline enantiomers. The CD signal was preliminarily attributed to coordination induction between chiral N-Boc-proline and the Eu(III) complex moiety. The linear regression analysis of CD sensing shows a good agreement between the magnitude of molar ellipticity and concentration of chiral N-Boc-l or d-proline, which indicates this kind Eu(III)-containing achiral polymer complex can be used as a chiral probe for enantioselective recognition of N-Boc-l or d-proline enantiomers based on Cotton effect of CD spectra.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Chiral ionic liquids derived from natural amino acids are shown to be green and efficient media for direct asymmetric aldol reactions at room temperature catalyzed by (S)-proline. The corresponding aldol products were obtained with moderate to good enantioselectivities. A transfer of chirality from the chiral reaction media has been observed as well as the participation of match/mismatch interactions of the chiral medium with both enantiomers of proline. Moreover, these catalytic systems were easily recovered by simple filtration, and studies on their reuse have demonstrated that recycling is possible for at least four runs with only a slight reduction in activity. Copyright

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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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The present invention provides compounds of formula (I): compositions comprising such compounds; the use of such compounds in therapy (such as asthma or COPD); and methods of treating patients with such compounds; wherein R1 – R11 are as defined herein.

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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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In a recent series of papers, Miller and co-workers were able to show that His(pi-Me)-based, terminally protected peptides are potent catalysts of the asymmetric acyl transfer reaction, useful for the kinetic resolution of alcohols. In a structure-supporting solvent, one of the most active compounds, an Aib-containing tetrapeptide, is folded in a doubly intramolecularly H-bonded beta-hairpin motif incorporating a type-II? beta-turn conformation. In this work, we have expanded the study of the Miller tetrapeptide by examining a set of analogues and shorter sequences (dipeptide amides), characterized by chiral Calpha-tetrasubstituted alpha-amino acids of diverging bulkiness and optical configuration. Peptide synthesis in solution, conformational analysis by FT-IR absorption and 1H NMR techniques, and screening of catalytic activity as well have been performed. Our results confirm the close relationship between the beta-hairpin 3D-structure and the catalytic activity of the peptides. A tetrapeptide analogue slightly more selective than the Miller compound has been found. However, the terminally protected, industrially more appealing, dipeptide amides are poorly effective.

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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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A novel and facile method for the synthesis of 4H-cyclopenta[c]pyrrolo[1,2- b] isoquinolin-2(3H)-one has been developed by employing the [2, 3] Stevens rearrangement of methyl N-allyl-N-benzylpyrrolidine 2-carboxylate to methyl 2-allyl-l-benzyl-pyrrolidine 2-carboxylate and acid-lactonisation as key transformations. The synthetic strategy from readily available materials provided a model skeletal analogue of cephalotaxine and should have general applicability in the synthesis of Cephalotaxus alkaloids.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Chemical investigation of a benthic marine cyanobacterium yielded the anticancer agent dolastatin 15, originally isolated from a mollusk. Dolastatin 15 is a microtubule-destabilizing agent with analogues undergoing clinical evaluation. Profiling against a panel of isogenic HCT116 colorectal cancer cells showed remarkable differential cytotoxicity against the parental cells over isogenic cells lacking HIF or other key players in the pathway, including oncogenic KRAS and VEGF. Dolastatin 15 displayed an antivascularization effect in human endothelial cells and in zebrafish vhl mutants with activated Hif, thus signifying its clinical potential as a treatment for solid tumors with an angiogenic component. Global transcriptome analysis with RNA sequencing suggested that dolastatin 15 could affect other major cancer pathways that might not directly involve tubulin or HIF. The identification of the true producer of a clinically relevant agent is important for sustainable supply, as is understanding the biosynthesis, and future genetic manipulation of the biosynthetic gene cluster for analogue production.

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Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Reliable determination of the enantiomeric excess of free amino acids can be obtained by measuring the induced circular dichroism of a multicomponent assembly formed by a modified tris(2-pyridylmethyl)amine ligand, a zinc salt, and the amino acid of interest. The systems furnish reliable information for all natural amino acids.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Enantiopure diarylmethanols, propargylic and allylic alcohols are important building blocks for the synthesis of a plethora of natural products and pharmaceutically relevant compounds. Among several methods employed for their synthesis, the enantioselective addition of diorganozinc compounds to carbonyl compounds in the presence of appropriate ligands becomes increasingly significant. In this comprehensive review, methods based on the use of readily available diethyl- and dimethylzinc for the formation of more complex compounds are compared and discussed. Available data on the mechanisms and transition states of reactions are presented.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI