- 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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- Combined Photoredox/Enzymatic C?H Benzylic Hydroxylations
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Chemical transformations that install heteroatoms into C?H bonds are of significant interest because they streamline the construction of value-added small molecules. Direct C?H oxyfunctionalization, or the one step conversion of a C?H bond to a C?O bond, could be a highly enabling transformation due to the prevalence of the resulting enantioenriched alcohols in pharmaceuticals and natural products,. Here we report a single-flask photoredox/enzymatic process for direct C?H hydroxylation that proceeds with broad reactivity, chemoselectivity and enantioselectivity. This unified strategy advances general photoredox and enzymatic catalysis synergy and enables chemoenzymatic processes for powerful and selective oxidative transformations.
- Betori, Rick C.,May, Catherine M.,Scheidt, Karl A.
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p. 16490 - 16494
(2019/11/03)
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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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- The influence of substitution at aromatic part of 1,2,3,4-tetrahydroisoquinoline on in vitro and in vivo 5-HT1A/5-HT2A receptor activities of its 1-adamantoyloaminoalkyl derivatives
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Further structure-activity relationship (SAR) studies with the 1,2,3,4-tetrahydroisoquinoline (THIQ) class of 5-HT1A ligands led to the synthesis of new 1-adamantoyloaminoalkyl derivatives. The impact of substituent variations in the aromatic part of THIQ moiety on 5-HT1A and 5-HT2A receptor affinities, as well as in vivo functional properties of the investigated compounds were discussed. It was found that modification reduced the binding affinity for 5-HT1A receptors (in comparison with unsubstituted THIQ derivatives); however, the majority of new compounds still remained potent 5-HT1A ligands (Ki = 4.9-46 nM) and most of them showed features of partial agonists of postsynaptic 5-HT1A receptors. At the same time, their 5-HT2A receptor affinity was slightly increased (Ki = 40-1475 nM), which resulted in a loss of 5-HT2A/5-HT1A selectivity. 5-Br,8-OCH3 derivative - the most potent, mixed 5-HT1A/5-HT2A ligand - produced activation of presynaptic 5-HT1A receptors and showed properties of a 5-HT2A receptor antagonist. Copyright
- Bojarski, Andrzej J,Mokrosz, Maria J,Minol, Sijka Charakchieva,Koziol, Aneta,Wesolowska, Anna,Tatarczynska, Ewa,Klodzinska, Aleksandra,Chojnacka-Wojcik, Ewa
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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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- Method of treating nausea and vomiting with certain substituted-phenylalkylamino (and aminoacid) derivatives and other serotonin depleting agents
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A method for the treatment of emesis in a mammal, which method comprises administering to said mammal an emesis inhibiting amount of a compound which depletes serotonin in the brain of mammals; among which are compounds having the formula: STR1 wherein, R is selected from hydrogen, loweralkyl, trifluoromethyl, carboxyl, or loweralkoxycarbonyl; R1 and R2 are hydrogen or loweralkyl; Z is trifluoromethyl or halogen; the optical isomers and pharmaceutically acceptable salts thereof; two of the preferred compounds of the invention are fenfluramine and norfenfluramine.
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- Synthesis of Fused Heterocycles: 1,2,3,4-Tetrahydroisoquinolines and Ring Homologues via Sulphonamidomethylation
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The title heterocycles (3) have been obtained by a two-step synthesis; namely an initial intramolecular sulphonamidomethylation of N-aralkylsulphonamides (1) in acid media followed by desulphonylation of compounds (2) under moderate conditions, either by reduction or acid hydrolysis.Generally both steps gave good or high yields of compounds (3) variously substituted in the aromatic ring and with a six-, seven-, or eight-membered heterocyclic ring.
- Orazi, Orfeo O.,Corral, Renee A.,Giaccio, Hector
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p. 1977 - 1982
(2007/10/02)
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- Diazaestrones and analogs. I. Pharmacological study and synthesis of heterosteroid analogs to establish structure-analgesic activity relationships
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With the intention of showing the effect, about pharmacological properties, in replacing two estron asymetric carbon by nitrogen atoms and removal of angular methyl from steroid, stereospecific synthesis of 8,13-diazaestron and several substituted similar compounds was realized from β-1-(succinimidoethyl)-dihydroisoquinolines, precursors of a C open ring synthesis. The splitting of the 2-methoxydiazaestron methyl ester was carried out by mean of binaphthylphosphoric acid, and synthesis of several modified analogs of heterosteroid, was carried out to determine the effect of aromatic ring reduction, lactamic carbonyl reduction, and distance between 8 and 13 nitrogen atoms, about pharmacological activity. Hormonal, spasmolytic and analgesic activities were studied, good results were observed in analgesic activity.
- Hocquaux,Marcot,Redeuilh,et al.
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p. 319 - 329
(2007/10/02)
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