- Bi-enzymatic Conversion of Cinnamic Acids to 2-Arylethylamines
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The conversion of carboxylic acids, such as acrylic acids, to amines is a transformation that remains challenging in synthetic organic chemistry. Despite the ubiquity of similar moieties in natural metabolic pathways, biocatalytic routes seem to have been overlooked for this purpose. Herein we present the conception and optimisation of a two-enzyme system, allowing the synthesis of β-phenylethylamine derivatives from readily-available ring-substituted cinnamic acids. After characterisation of both parts of the reaction in a two-step approach, a set of conditions allowing the one-pot biotransformation was optimised. This combination of a reversible deaminating and irreversible decarboxylating enzyme, both specific for the amino acid intermediate in tandem, represents a general method by which new strategies for the conversion of carboxylic acids to amines could be designed.
- Weise, Nicholas J.,Thapa, Prasansa,Ahmed, Syed T.,Heath, Rachel S.,Parmeggiani, Fabio,Turner, Nicholas J.,Flitsch, Sabine L.
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p. 995 - 998
(2020/01/21)
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- Biocatalytic Formal Anti-Markovnikov Hydroamination and Hydration of Aryl Alkenes
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Biocatalytic anti-Markovnikov alkene hydroamination and hydration were achieved based on two concepts involving enzyme cascades: epoxidation-isomerization-amination for hydroamination and epoxidation-isomerization-reduction for hydration. An Escherichia coli strain coexpressing styrene monooxygenase (SMO), styrene oxide isomerase (SOI), ω-transaminase (CvTA), and alanine dehydrogenase (AlaDH) catalyzed the hydroamination of 12 aryl alkenes to give the corresponding valuable terminal amines in high conversion (many ≥86%) and exclusive anti-Markovnikov selectivity (>99:1). Another E. coli strain coexpressing SMO, SOI, and phenylacetaldehyde reductase (PAR) catalyzed the hydration of 12 aryl alkenes to the corresponding useful terminal alcohols in high conversion (many ≥80%) and very high anti-Markovnikov selectivity (>99:1). Importantly, SOI was discovered for stereoselective isomerization of a chiral epoxide to a chiral aldehyde, providing some insights on enzymatic epoxide rearrangement. Harnessing this stereoselective rearrangement, highly enantioselective anti-Markovnikov hydroamination and hydration were demonstrated to convert α-methylstyrene to the corresponding (S)-amine and (S)-alcohol in 84-81% conversion with 97-92% ee, respectively. The biocatalytic anti-Markovnikov hydroamination and hydration of alkenes, utilizing cheap and nontoxic chemicals (O2, NH3, and glucose) and cells, provide an environmentally friendly, highly selective, and high-yielding synthesis of terminal amines and alcohols.
- Wu, Shuke,Liu, Ji,Li, Zhi
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p. 5225 - 5233
(2017/08/17)
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- Preparation and characterization of primary amines by potassium borohydride-copper chloride system from nitriles
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Nitriles undergo reduction to primary amines under optimized conditions at 50 °C using 0.25 equiv of copper chloride and 3.0 equiv of potassium borohydride in 80 % isopropanol. The aromatic and aralkyl nitriles could be effectively reduced in yield ranging from 60 to 90 %.
- Jiang, Han,Hu, Jialei,Xu, Xinliang,Zhou, Yifeng
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p. 3564 - 3566
(2015/12/30)
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- DOLASTATIN-10 DERIVATIVE, METHOD OF PRODUCING SAME AND ANTICANCER DRUG COMPOSITION CONTAINING SAME
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The present invention provides a dolastatin-10 derivative having excellent anticancer activity, a method of producing the same and anticancer drug composition containing the same as an active ingredient.
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Paragraph 0089; 0090; 0091; 0092; 0093; 0094
(2015/07/15)
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- PRODUCTION OF INDUCED PLURIPOTENT STEM CELLS
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The present disclosure relates to methods and compositions that improve the in vitro production of induced pluripotent stem cells through the use of compounds that promote degradation of p53. The disclosure also relates to compositions and methods for the treatment of cancer, pancreatitis and intracellular pathogens.
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Page/Page column 63-64
(2012/06/30)
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- The catalytic potential of Coptis japonica NCS2 revealed - Development and utilisation of a fluorescamine-based assay ETI
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The versatility and potential of a norcoclaurine synthase (NCS) from Coptis japonica NCS2 has been investigated, together with the development and application of a novel fluorescence-based high-throughput assay using nearly forty amines/aldehydes. The stereocontrol exerted by CjNCS2 on selected non-natural substrates has been determined, where the tetrahydroisoquinolines (THIAs) were formed as the (1S)-isomer in >95% ee, as observed with the natural product norcoclaurine. Docking calculations involving THIA mechanism intermediates, utilising the reported Thalictrum flavum NCS X-ray crystallographic structure, were carried out and combined with the CjNCS2 screening results to further understand the mode of action of NCS. These findings suggested that in addition to the key active-site residues K122 and E110, D141 is also mechanistically essential for the enzymatic transformation. The exceptional tolerance of NCS towards aldehyde substrates is furthermore supported by our proposed mechanism in which the aldehydes protrude out of the enzymatic pocket. Copyright
- Pesnot, Thomas,Gershater, Markus C.,Ward, John M.,Hailes, Helen C.
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p. 2997 - 3008
(2013/01/15)
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- POTENT SMALL MOLECULE INHIBITORS OF AUTOPHAGY, AND METHODS OF USE THEREOF
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Certain aspects of the invention relates to small molecule autophagy inhibitors, and their use for treatment and prevention of cancers and acute pancreatitis. As disclosed herein, a small molecule inhibitor of autophagy was been identified from an image-based screen in a known bioactive library. It was found that this autophagy inhibitor functions by promoting the degradation of type III PI3 kinase complex which is required for initiating autophagy. Medicinal chemistry studies led to small molecular autophagy inhibitors with improved potency and selectivity.
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Page/Page column 58
(2011/02/24)
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- Tetracyclic benzimidazole derivatives and combinatorial libraries thereof
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The present invention relates to novel tetracyclic benzimidazole derivative compounds of the following formula: wherein R1to R10have the meanings described in here. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing tetracyclic benzimidazole derivative compounds.
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- 2-aminopyridine derivatives and combinatorial libraries thereof
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The present invention relates to novel 2-aminopyridine derivative compounds of the following formula: wherein R1to R5have the meanings provided herein. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing 2-aminopyridine derivative compounds.
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- Process for preparing fluorine-containing phenethylamines and novel fluorine-containing β-iminovinyl-and β-iminoethylbenzenes
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The present invention relates to a process for preparing fluorine-containing phenethylamines which is characterized in that, in a first step, a substituted bromobenzene is reacted with an N-vinylimide in the presence of a palladium catalyst, in a second step, the resulting substituted β-iminovinylbenzene is hydrogenated catalytically and in a third step, the substituted β-iminovinylbenzene obtained in the second step is cleaved. This process also provides access to novel β-iminovinyl- and β-iminoethylbenzenes.
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- Process for the preparation of (8As,12AS,13AS)-decahydroisoquino ((2,1-G) (1,6)-naphthyridin-8-one derivatives
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The invention provides a process for preparing single enantiomers of compounds represented by the formula: STR1 and chiral acid addition salts thereof; wherein: X and Y are independently hydrogen; lower alkyl; lower alkoxy; or halo; or X and Y taken together is methylenedioxy or ethylene-1,2-dioxy; which includes reduction of a compound represented by the formula: STR2 to give a mixture of stereoisomers represented by the formula: STR3 wherein each wavy line independently represents a bond in either the α or β position; followed by dissolving the mixture of stereoisomers and a chiral resolving acid in a suitable solvent and allowing the solution to crystallize, giving a salt of the desired enantiomer.
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- Inactivation of Leukocyte Elastase by Aryl Azolides and Sulfonate Salts. Structure-Activity Relationship Studies
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The inhibitory activity of a series of aryl azolides and sulfonate salts toward human leukocyte elastase is reported.Several of the compounds were found to be potent inhibitors of the enzyme.Active compounds were obtained only when the specificity group and the reactive moiety were separated by a two-carbon chain.The introduction of hydrophobic groups enhanced the inhibitory activity of these compounds, with the exception of the sulfonate salts.The nature of the leaving group had had a profound effect on inhibitory activity, with compounds 23 and 26 being the most active (kobsd/ = 11722 and 13500 M-1 s-1, respectively).
- Groutas, W. C.,Brubaker, M. J.,Zandler, M. E.,Mazo-Gray, V.,Rude, S. A.,et al.
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p. 1302 - 1305
(2007/10/02)
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