Discovery of 1-Phenyl-1,2,3,4-tetrahydroisoquinoline

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Advances in ultrahigh-throughput screening for directed enzyme evolution

Enzymes are versatile catalysts and their synthetic potential has been recognized for a long time. In order to exploit their full potential, enzymes often need to be re-engineered or optimized for a given application. (Semi-) rational design has emerged as a powerful means to engineer proteins, but requires detailed knowledge about structure function relationships. In turn, directed evolution methodologies, which consist of iterative rounds of diversity generation and screening, can improve an enzyme’s properties with virtually no structural knowledge. Current diversity generation methods grant us access to a vast sequence space (libraries of >1012 enzyme variants) that may hide yet unexplored catalytic activities and selectivity. However, the time investment for conventional agar plate or microtiter plate-based screening assays represents a major bottleneck in directed evolution and limits the improvements that are obtainable in reasonable time. Ultrahigh-throughput screening (uHTS) methods dramatically increase the number of screening events per time, which is crucial to speed up biocatalyst design, and to widen our knowledge about sequence function relationships. In this review, we summarize recent advances in uHTS for directed enzyme evolution. We shed light on the importance of compartmentalization to preserve the essential link between genotype and phenotype and discuss how cells and biomimetic compartments can be applied to serve this function. Finally, we discuss how uHTS can inspire novel functional metagenomics approaches to identify natural biocatalysts for novel chemical transformations.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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Nonconventional carbon additions to azomethines. Aryl amination/idoline synthesis by direct aryl radical addition to azomethine nitrogen

(matrix presented) The generality of a new method for aryl amination has been defined. Ketimines derived from o-bromophenethylamine cyclize to the N-substituted indoline when treated with nBu3SnH and a radical initiator. The pH-neutral conditions tolerate base- and acid-sensitive functionality. The observed regioselectivity is nonconventional for addition reactions involving carbon radicals and carbon-heteroatom pi-bonds.

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Reference£º
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Some scientific research about 22990-19-8

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3-Hydroxypyrroles and 1H-Pyrrol-3(2H)-ones. Part 3. Pyrrolones from Pyrolyses of Aminomethylene Meldrum’s Acid Derivatives: Loss of Chirality at the Site of Hydrogen Transfer.

Pyrolysis of the diastereoisomeric Meldrum’s acid derivatives (4) and (5), or of the chiral derivatives (6), (7), and (9), gives 2,2-disubstituted 1H-pyrrol-3(2H)-ones in which there is loss of configuration at the reaction site .The extent of configuration loss is greater if the reaction site is part of a ring.These results are explained by a two-step, hydrogen-transfer-cyclisation mechanism, following initial generation of a methyleneketene.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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22990-19-8, Chemistry can be defined as the study of matter and the changes it undergoes. You¡¯ll sometimes hear it called the central science because it is the connection between physics and all the other sciences, starting with biology.22990-19-8, Name is 1-Phenyl-1,2,3,4-tetrahydroisoquinoline, molecular formula is C15H15N, introducing its new discovery.

Simultaneous engineering of an enzyme’s entrance tunnel and active site: The case of monoamine oxidase MAO-N

A new directed evolution approach is presented to enhance the activity of an enzyme and to manipulate stereoselectivity by focusing iterative saturation mutagenesis (ISM) simultaneously on residues lining the entrance tunnel and the binding pocket. This combined mutagenesis strategy was applied successfully to the monoamine oxidase from Aspergillus Niger (MAO-N) in the reaction of sterically demanding substrates which are of interest in the synthesis of chiral pharmaceuticals based on the benzo-piperidine scaffold. Reversal of enantioselectivity of Turner-type deracemization was achieved in the synthesis of (S)-1,2,3,4-tetrahydro-1-methyl-isoquinoline, (S)-1,2,3,4-tetrahydro-1-ethylisoquinoline and (S)-1,2,3,4-tetrahydro-1-isopropylisoquinoline. Extensive molecular dynamics simulations indicate that the altered catalytic profile is due to increased hydrophobicity of the entrance tunnel acting in concert with the altered shape of the binding pocket.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Simple exploration of 1-Phenyl-1,2,3,4-tetrahydroisoquinoline

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Free radical-mediated aryl amination and its use in a convergent [3 + 2] strategy for enantioselective indoline alpha-amino acid synthesis

The scope of aryl radical additions to the nitrogen of azomethines is described. Aryl, trifluoromethyl alkyl, and alpha,beta-unsaturated ketimines engage in regioselective aryl-nitrogen bond formation via 5-exo cyclizations of an aryl radical to azomethine nitrogen. Selectivity for carbon-nitrogen over carbon-carbon bond formation is generally high (>95:5) and competes only with direct aryl radical reduction by stannane (0-10%). alpha-Ketoimines are a promising new class of carbon radical acceptors for which no competitive aryl radical reduction is observed. The reaction conditions are pH-neutral and are therefore among the mildest methods available for amination of an aromatic ring. The ketimines examined did not suffer from competitive reduction by stannane, offering an advantage over the use of diazo and azide functional groups as nitrogen sources for carbon radicals. The free radical-mediated aryl amination was sequenced with the O’Donnell phase transfer-catalyzed enantioselective alkylation strategy of glycinyl imine to provide either enantiomer of indoline alpha-amino acids with high ee. These new constrained phenyl alanine derivatives are now readily available for evaluation across a variety of applications.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Awesome and Easy Science Experiments about 1-Phenyl-1,2,3,4-tetrahydroisoquinoline

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PROCESS FOR PREPARATION OF ENANTIOMERICALLY PURE (S)-1-PHENYI-1,2,3,4- TETRAHYDROISOQUINOLINE

Process for preparation of (S)-1 -phenyl-1, 2,3, 4-tetrahydroisoquinoline is characterized in that 1-phenyl-1,2,3, 4-tetrahydroisoquinoline is reacted with D-(-)- tartaric acid in a solvent system consisting of methanol and water, preferably at 3.3:1 to 1 :1 volume ratio, the crystallization mixture is left for crystallization and (S)-1-phenyl-1,2,3, 4-tetrahydroisoquinoline is released from obtained crystalline diastereoisomeric salt according to standard procedures. (S)-1-Phenyl- 1,2,3, 4-tetrahydroisoquinoline is the intermediate in enantiomeric synthesis of solifenacin.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Some tips on 1-Phenyl-1,2,3,4-tetrahydroisoquinoline

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As a common heterocyclic compound, it belongs to tetrahydroisoquinoline compound, name is 1-Phenyl-1,2,3,4-tetrahydroisoquinoline, and cas is 22990-19-8, its synthesis route is as follows.,22990-19-8

1 -phenyl-1 ,2,3,4-tetrahydroisoquinoline (100 g) was placed into a round bottom flask and methanol (400 mL) was added and stirred for about 5 minutes. The reaction mass was then heated to about 400C, and D-(-)-tartaric acid (71.6 g) was added. The reaction mass was further heated to about 64C and maintained for about 2 hours. The reaction mass was then allowed to cool to about 28C and ethyl acetate (200 mL) was added. The reaction mass was maintained at about 28C for about 20 minutes, and then filtered. The filtered solid was washed with methanol (100 mL) and the wet solid was dried at about 55C for about 1 hour, 20 minutes.The dry material was placed into a round bottom flask and methanol (270 mL) was added. The reaction mass was heated to about 64C and maintained for about 1 hour. The reaction mass was then allowed to cool to about 28C and ethyl acetate (136 mL) was added. The reaction mass was maintained at about 28C for about 1 hour and the solid was filtered and washed with methanol (68 ml_). The wet solid was dried at about 500C for about 1 hour. The dry solid was placed into a round bottom flask and water (938 ml_) was added. The mixture was stirred for about 10 minutes and the pH of the mixture is adjusted to about 8-9 using 10% aqueous sodium hydroxide solution. The mixture was stirred at about 28C for about 1 hour and then filtered. The filtered solid was washed with water (125 ml_) and dried at about 53C for about 9 hours to get 35.9 g of the title compound. Purity by HPLC: 99.24% by weight. Chiral purity by HPLC: 99.64% by weight.

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Reference£º
Patent; DR. REDDY’S LABORATORIES LTD.; DR. REDDY’S LABORATORIES, INC.; WO2008/128028; (2008); A2;,
Tetrahydroisoquinoline – Wikipedia
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Application of 5-Phenylimidazolidine-2,4-dione

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A common heterocyclic compound, the tetrahydroisoquinoline compound, name is 1-Phenyl-1,2,3,4-tetrahydroisoquinoline,cas is 22990-19-8, mainly used in chemical industry, its synthesis route is as follows.

Racemic mixture of 1 -phenyl- 1, 2,3, 4-tetrahydroisoquinoline (40 g, 191 mmol) and D-(-)-tartaric acid (28.61 g, 191 mmol, ee 99%) are suspended in methanol (240 niL). The solution is heated to reflux, until the whole amount of solid is completely dissolved. The heating bath is being removed and to the clear solution water (120 mL) is added; the resulting mixture is left at ambient temperature (240C) for 24 h. Crystalline solid is filtered off (21.45 g). -17.02 (c=l%, H2O).Obtained crystalline solid is suspended in the mixture of 10% NaOHaq (120 mL) and ethyl acetate (50 mL), the solution is stirred at ambient temperature (240C) for about 10 min. until the whole amount of solid is dissolved. The reaction mixture is transferred into separatory flask, organic layer is separated and water phase is extracted with ethyl acetate (2×30 mL). Combined organic extracts are washed with water (1×40 mL), dried and condensed under vacuum to dryness. (S)-1-Phenyl- 1,2,3, 4-tetrahydroisoquinoline is obtained as crystalline solid (12 g, 30%), of enantiomeric excess ee = 100%. Chemical purity (HPLC): 99.96%; [alpha]25D = 38.20 (c=l%, CH2Cl2).

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Reference£º
Patent; ZAKLADY FARMACEUTYCZNE POLPHARMA SA; WO2009/142521; (2009); A1;,
Tetrahydroisoquinoline – Wikipedia
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

Extracurricular laboratory: Synthetic route of 22990-19-8

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1-Phenyl-1,2,3,4-tetrahydroisoquinoline, cas is 22990-19-8, it is a common heterocyclic compound, the tetrahydroisoquinoline compound, its synthesis route is as follows.

REFERENCE EXAMPLE 1 To a 130 ml dichloromethane solution containing 6.28 g of 1-phenyl-1,2,3,4-tetrahydroisoquinoline and 3.34 g of triethylamine, 3.1 ml of ethyl chloroformate was added dropwise under ice-cooling, followed by stirring at room temperature overnight. The reaction solution was washed successively with water, 1N hydrochloric acid, water and brine and then dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, thereby 10.58 g of ethyl 1-phenyl-1,2,3,4-tetrahydro-2-isoquinolinecarboxylate was obtained as pale yellow oil. Infrared absorption spectrum numax(neat)cm-1: 1700, 1430, 1296, 1230, 1122. Nuclear magnetic resonance spectrum (CDCl3, TMS internal standard); delta: 1.29 (3H, t, J=7.3 Hz), 2.75-3.45 (3H, m), 3.90-4.40 (1H, m), 4.21 (2H, q, J=7.3 Hz), 6.38 (1H, s), 6.95-7.45 (9H, m).

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Reference£º
Patent; Yamanouchi Pharmaceutical Co., Ltd.; US6017927; (2000); A;,
Tetrahydroisoquinoline – Wikipedia
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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Name is 1-Phenyl-1,2,3,4-tetrahydroisoquinoline, as a common heterocyclic compound, it belongs to tetrahydroisoquinoline compound, and cas is 22990-19-8, its synthesis route is as follows.,22990-19-8

General procedure: Pd/C (254 mg, 0.12 mmol) and K3PO4*3H2O (16 mg, 0.06mmol) were placed in a Schlenk tube followed by acetonitrile(1 mL), and the resulting mixture was stirred at room temperaturefor 10 min. A solution of 1-substituted-1,2,3,4- tetrahydroisoquinoline(0.30 mmol) in acetonitrile (4 mL) was thenadded to the reaction mixture, and the Schlenk tube was carefullyand quickly vacuum purged before being filled with oxygenusing an oxygen balloon. The reaction mixture was thenstirred at 60 C until the 1-substituted-1,2,3,4- tetrahydroisoquinolinehad been completely consumed (as determined byTLC analysis). Upon completion of the reaction, the mixturewas slowly cooled to room temperature and filtered throughdiatomite to remove the Pd/C catalyst. The filtrate was thenconcentrated in vacuo to give the crude product as a residue,which was purified by flash chromatography over silica geleluting with petroleum ether and ethyl acetate to give the imineproduct 2. 1-Phenyl-3,4-dihydroisoquinoline (2a): 86% yield, known compound [ 54 ], yellow oil, Rf = 0.75 (ethyl acetate). 1H NMR (400 MHz, CDCl3) delta = 7.60-7.56 (m, 2H), 7.44-7.35 (m, 4H), 7.26-7.21 (m, 3H), 3.85-3.82 (m, 2H), 2.80-2.77 (m, 2H); 13C NMR (100 MHz, CDCl3) delta = 167.3, 139.0, 138.9, 130.7, 129.3, 128.9, 128.8, 128.1, 127.9, 127.4, 126.6, 47.7, 26.3.

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Reference£º
Article; Ji, Yue; Chen, Mu-Wang; Shi, Lei; Zhou, Yong-Gui; Cuihua Xuebao/Chinese Journal of Catalysis; vol. 36; 1; (2015); p. 33 – 39;,
Tetrahydroisoquinoline – Wikipedia
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem