- Markovnikov Wacker-Tsuji Oxidation of Allyl(hetero)arenes and Application in a One-Pot Photo-Metal-Biocatalytic Approach to Enantioenriched Amines and Alcohols
-
The Wacker-Tsuji aerobic oxidation of various allyl(hetero)arenes under photocatalytic conditions to form the corresponding methyl ketones is presented. By using a palladium complex [PdCl2(MeCN)2] and the photosensitizer [Acr-Mes]ClO4 in aqueous medium and at room temperature, and by simple irradiation with blue led light, the desired carbonyl compounds were synthesized with high conversions (>80%) and excellent selectivities (>90%). The key process was the transient formation of Pd nanoparticles that can activate oxygen, thus recycling the Pd(II) species necessary in the Wacker oxidative reaction. While light irradiation was strictly mandatory, the addition of the photocatalyst improved the reaction selectivity, due to the formation of the starting allyl(hetero)arene from some of the obtained by-products, thus entering back in the Wacker-Tsuji catalytic cycle. Once optimized, the oxidation reaction was combined in a one-pot two-step sequential protocol with an enzymatic transformation. Depending on the biocatalyst employed, i. e. an amine transaminase or an alcohol dehydrogenase, the corresponding (R)- and (S)-1-arylpropan-2-amines or 1-arylpropan-2-ols, respectively, could be synthesized in most cases with high yields (>70%) and in enantiopure form. Finally, an application of this photo-metal-biocatalytic strategy has been demonstrated in order to get access in a straightforward manner to selegiline, an anti-Parkinson drug. (Figure presented.).
- Albarrán-Velo, Jesús,Gotor-Fernández, Vicente,Lavandera, Iván
-
supporting information
p. 4096 - 4108
(2021/08/19)
-
- Direct Access to Primary Amines from Alkenes by Selective Metal-Free Hydroamination
-
Direct and selective synthesis of primary amines from easily available precursors is attractive yet challenging. Herein, we report the rapid synthesis of primary amines from alkenes via metal-free regioselective hydroamination at room temperature. Ammonium carbonate was used as ammonia surrogate for the first time, allowing for efficient conversion of terminal and internal alkenes into linear, α-branched, and α-tertiary primary amines under mild conditions. This method provides a straightforward and powerful approach to a wide spectrum of advanced, highly functionalized primary amines which are of particular interest in pharmaceutical chemistry and other areas.
- Du, Yi-Dan,Chen, Bi-Hong,Shu, Wei
-
supporting information
p. 9875 - 9880
(2021/03/29)
-
- ASPARAGINE DERIVATIVES AND METHODS OF USE THEREOF
-
The present invention relates to compounds of formulas (A) and (I), pharmaceutically acceptable salts thereof, and solvates of any of them, pharmaceutical compositions comprising them, methods of preparation thereof, intermediate compounds useful for the preparation thereof, and methods of treatment or prophylaxis of diseases, in particular cancer, such as colorectal cancer, using these. (A) (I)
- -
-
-
- Transaminase-mediated synthesis of enantiopure drug-like 1-(3′,4′-disubstituted phenyl)propan-2-amines
-
Transaminases (TAs) offer an environmentally and economically attractive method for the direct synthesis of pharmaceutically relevant disubstituted 1-phenylpropan-2-amine derivatives starting from prochiral ketones. In this work, we report the application of immobilised whole-cell biocatalysts with (R)-transaminase activity for the synthesis of novel disubstituted 1-phenylpropan-2-amines. After optimisation of the asymmetric synthesis, the (R)-enantiomers could be produced with 88-89% conversion and >99% ee, while the (S)-enantiomers could be selectively obtained as the unreacted fraction of the corresponding racemic amines in kinetic resolution with >48% conversion and >95% ee. This journal is
- Lakó, ágnes,Mendon?a, Ricardo,Molnár, Zsófia,Poppe, László
-
p. 40894 - 40903
(2020/11/23)
-
- ENVIRONMENTALLY-FRIENDLY HYDROAZIDATION OF OLEFINS
-
The present invention provides processes for the synthesis of organic azides, intermediates for the production thereof, and compositions related thereto.
- -
-
Page/Page column 63; 71-72
(2020/01/24)
-
- Stereoselective Synthesis of 1-Arylpropan-2-amines from Allylbenzenes through a Wacker-Tsuji Oxidation-Biotransamination Sequential Process
-
Herein, a sequential and selective chemoenzymatic approach is described involving the metal-catalysed Wacker-Tsuji oxidation of allylbenzenes followed by the amine transaminase-catalysed biotransamination of the resulting 1-arylpropan-2-ones. Thus, a series of nine optically active 1-arylpropan-2-amines were obtained with good to very high conversions (74–92%) and excellent selectivities (>99% enantiomeric excess) in aqueous medium. The Wacker-Tsuji reaction has been exhaustively optimised searching for compatible conditions with the biotransamination experiments, using palladium(II) complexes as catalysts and iron(III) salts as terminal oxidants in aqueous media. The compatibility of palladium/iron systems for the chemical oxidation with commercially available and made in house amine transaminases was analysed, finding ideal conditions for the development of a general and stereoselective cascade sequence. Depending on the selectivity displayed by selected amine transaminase, it was possible to produce both 1-arylpropan-2-amines enantiomers under mild reaction conditions, compounds that present therapeutic properties or can be employed as synthetic intermediates of chiral drugs from the amphetamine family. (Figure presented.).
- González-Martínez, Daniel,Gotor, Vicente,Gotor-Fernández, Vicente
-
p. 2582 - 2593
(2019/05/15)
-
- AMPHETAMINE CONTROLLED RELEASE, PRODRUG, AND ABUSE-DETERRENT DOSAGE FORMS
-
The invention also relates to pharmaceutical compositions comprising highly pure amphetamine and amphetamine-class compounds resulting from the synthesis of chiral and racemic amphetamine derivatives by stereospecific, regioselective cuprate addition reaction with aziridine phosphoramidate compounds, and to methods of manufacturing, delivering, and using the amphetamine compounds resulting from the synthesis of chiral and racemic amphetamine derivatives by stereospecific, regioselective cuprate addition reaction with aziridine phosphoramidate compounds.
- -
-
Paragraph 0397; 0398
(2018/09/16)
-
- Ligand-Enabled meta-Selective C-H Arylation of Nosyl-Protected Phenethylamines, Benzylamines, and 2-Aryl Anilines
-
A Pd-catalyzed, meta-selective C-H arylation of nosyl-protected phenethylamines and benzylamines is disclosed using a combination of norbornene and pyridine-based ligands. Subjecting nosyl protected 2-aryl anilines to this protocol led to meta-C - H arylation at the remote aryl ring. A diverse range of aryl iodides are tolerated in this reaction, along with select heteroaryl iodides. Select aryl bromides bearing ortho-coordinating groups can also be utilized as effective coupling partners in this reaction. The use of pyridine ligands has allowed the palladium loading to be reduced to 2.5 mol %. Furthermore, a catalytic amount of 2-norbomene (20 mol %) to mediate this meta-C - H activation process is demonstrated for the first time. Utilization of a common protecting group as the directing group for meta-C-H activation of amines is an important feature of this reaction in terms of practical applications.
- Ding, Qiuping,Ye, Shengqing,Cheng, Guolin,Wang, Peng,Farmer, Marcus E.,Yu, Jin-Quan
-
supporting information
p. 417 - 425
(2017/05/16)
-
- Hybrid Organo- and Biocatalytic Process for the Asymmetric Transformation of Alcohols into Amines in Aqueous Medium
-
A hybrid organo- and biocatalytic system for the asymmetric conversion of racemic alcohols into amines was developed. Combining an organocatalyst, AZADO, an oxidant, NaOCl, and an enzyme, ω-transaminase, we implemented a one-pot oxidation-transamination sequential process in aqueous medium. The method showed broad substrate scope and was successfully applied to conventional secondary alcohols and sterically hindered β-substituted cycloalkanols, where a highly stereoselective dynamic asymmetric bioamination enabled us to set up both contiguous stereocenters with very high enantio- and diastereomeric ratio (>90% yield, >99% ee, and up to 49:1 dr).
- Liardo, Elisa,Ríos-Lombardía, Nicolás,Morís, Francisco,Rebolledo, Francisca,González-Sabín, Javier
-
p. 4768 - 4774
(2017/07/24)
-
- MOF-derived cobalt nanoparticles catalyze a general synthesis of amines
-
The development of base metal catalysts for the synthesis of pharmaceutically relevant compounds remains an important goal of chemical research. Here, we report that cobalt nanoparticles encapsulated by a graphitic shell are broadly effective reductive amination catalysts. Their convenient and practical preparation entailed template assembly of cobaltdiamine- dicarboxylic acid metal organic frameworks on carbon and subsequent pyrolysis under inert atmosphere.The resulting stable and reusable catalysts were active for synthesis of primary, secondary, tertiary, and N-methylamines (more than 140 examples).The reaction couples easily accessible carbonyl compounds (aldehydes and ketones) with ammonia, amines, or nitro compounds, and molecular hydrogen under industrially viable and scalable conditions, offering cost-effective access to numerous amines, amino acid derivatives, and more complex drug targets.
- Jagadeesh, Rajenahally V.,Murugesan, Kathiravan,Alshammari, Ahmad S.,Neumann, Helfried,Pohl, Marga-Martina,Radnik, J?rg,Beller, Matthias
-
p. 326 - 332
(2017/09/28)
-
- AMPHETAMINE CONTROLLED RELEASE, PRODRUG, AND ABUSE DETERRENT DOSAGE FORMS
-
The invention also relates to pharmaceutical compositions comprising highly pure amphetamine and amphetamine-class compounds resulting from the synthesis of chiral and racemic amphetamine derivatives by stereospecific, regioselective cuprate addition reaction with aziridine phosphoramidate compounds, and to methods of manufacturing, delivering, and using the amphetamine compounds resulting from the synthesis of chiral and racemic amphetamine derivatives by stereospecific, regioselective cuprate addition reaction with aziridine phosphoramidate compounds.
- -
-
-
- Method for synthesizing amphetamine drug intermediate 1-phenyl-2-aminopropane
-
The invention discloses a method for synthesizing an amphetamine drug intermediate 1-phenyl-2-aminopropane. The method is as below: adding propiophenone and molybdenum chloride powder in a mixed solution of 2,5-dimethyl benzylamine and p-ethylpropiophenone, conducting heating and pressure-increased reaction, cooling, eliminating air, filtering, and conducting vacuum distillation, washing, dehydration and recrystallization to obtain 1-phenyl-2-aminopropane. Compared to the synthesis method in the background, the synthetic method greatly shortens the reaction time, and significantly increases the yield; at the same time, the invention provides a novel synthetic route, and lays a good foundation to further improve the reaction yield.
- -
-
Paragraph 0020; 0021; 0022; 0023
(2017/01/19)
-
- DIRECT STEREOSPECIFIC SYNTHESIS OF UNPROTECTED AZIRIDINES FROM OLEFINS
-
A method for the direct stereospecific conversion of structurally diverse mono-, di-, tri- and tetra-substituted olefins to N-H, N-alkyl, N-cycloalkyl, or N-aralkyl aziridines using a hydroxylamine amination agent with transition metal catalyst. The method is operationally simple (i.e., one-pot), scalable and fast at ambient temperature.
- -
-
-
- Broadening the chemical scope of laccases: Selective deprotection of N-benzyl groups
-
Laccase from Trametes versicolor together with TEMPO has been found to be a very efficient system to deprotect N-benzylated primary amines, differing from previously described methods since it uses oxygen as a mild oxidant in aqueous medium. Chemoselective removal of the benzyl group was achieved with excellent yields when secondary amines and alcohol moieties were also present.
- Martínez-Montero, Lía,Díaz-Rodríguez, Alba,Gotor, Vicente,Gotor-Fernández, Vicente,Lavandera, Iván
-
supporting information
p. 2794 - 2798
(2015/05/27)
-
- Use of metal-accumulating plants for implementing chemical reactions
-
The use of metal-accumulating plants for implementing chemical reactions.
- -
-
Page/Page column 49; 50
(2015/10/28)
-
- USE OF COMPOSITIONS OBTAINED BY CALCINING PARTICULAR METAL-ACCUMULATING PLANTS FOR IMPLEMENTING CATALYTICAL REACTIONS
-
The use of metal-accumulating plants for implementing chemical reactions especially catalytical reactions.
- -
-
Paragraph 0787-0793
(2016/01/25)
-
- Direct stereospecific synthesis of unprotected N-H and N-Me aziridines from olefins
-
Despite the prevalence of the N-H aziridine motif in bioactive natural products and the clear advantages of this unprotected parent structure over N-protected derivatives as a synthetic building block, no practical methods have emerged for direct synthesis of this compound class from unfunctionalized olefins. Here, we present a mild, versatile method for the direct stereospecific conversion of structurally diverse mono-, di-, tri-, and tetrasubstituted olefins to N-H aziridines using O-(2,4-dinitrophenyl)hydroxylamine (DPH) via homogeneous rhodium catalysis with no external oxidants. This method is operationally simple (i.e., one-pot), scalable, and fast at ambient temperature, furnishing N-H aziridines in good-to-excellent yields. Likewise, N-alkyl aziridines are prepared from N-alkylated DPH derivatives. Quantum-mechanical calculations suggest a plausible Rh-nitrene pathway.
- Jat, Jawahar L.,Paudyal, Mahesh P.,Gao, Hongyin,Xu, Qing-Long,Yousufuddin, Muhammed,Devarajan, Deepa,Ess, Daniel H.,Kurti, Laszlo,Falck, John R.
-
-
- Simple access to elusive α-boryl carbanions and their alkylation: An umpolung construction for organic synthesis
-
The reaction of 1,1-bis(pinacolboronate) esters with alkyl halides can be effected by metal alkoxides and provides a strategy for the construction of organoboronate compounds. The reaction is found to occur by alkoxide-induced deborylation and generation of a boron-stabilized carbanion.
- Hong, Kai,Liu, Xun,Morken, James P.
-
supporting information
p. 10581 - 10584
(2014/08/18)
-
- Heterogeneous Ni catalyst for direct synthesis of primary amines from alcohols and ammonia
-
This paper reports the synthesis of primary amines from alcohols and NH3 by an Al2O3-supported Ni nanoparticle catalyst as the first example of heterogeneous and noble-metal-free catalytic system for this reaction without additional hydrogen sources under relatively mild conditions. Various aliphatic alcohols are tolerated, and turnover numbers were higher than those of Ru-based homogeneous catalysts. The catalyst was recoverable and was reused. The effects of the Ni oxidation states and the acid-base nature of support oxides on the catalytic activity are studied. It is clarified that the surface metallic Ni sites are the catalytically active species, and the copresence of acidic and basic sites on the support surface is also indispensable for this catalytic system.
- Shimizu, Ken-Ichi,Kon, Kenichi,Onodera, Wataru,Yamazaki, Hiroshi,Kondo, Junko N.
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p. 112 - 117
(2013/03/29)
-
- Enzymatic enantiomeric resolution of phenylethylamines structurally related to amphetamine
-
Both enantiomers of several phenylethylamines, structurally related to amphetamine, have been prepared in good yields and excellent enantiomeric purity by enzymatic kinetic resolution using CAL-B and ethyl methoxyacetate as the acyl donor. In the case of the 4-hydroxyderivative of amphetamine (compound 4i), the S enantiomer racemized possibly in a dynamic kinetic resolution (DKR) under the enzymatic conditions used. The Royal Society of Chemistry 2011.
- Munoz, Lourdes,Rodriguez, Anna M.,Rosell, Gloria,Bosch, M. Pilar,Guerrero, Angel
-
p. 8171 - 8177
(2012/01/04)
-
- Ring opening of pymisyl-protected aziridines with organocuprates
-
The pyrimidine-2-sulfonyl (pymisyl) group is introduced as a new protecting group that can be used to activate aziridines towards ring opening. It is readily introduced and removed under mild conditions. Regioselective ring opening of pymisyl-protected 2-methyl-aziridine with organocuprates gives the corresponding sulfonamides in high yields, and the pymisyl group can subsequently be removed upon treatment with a thiolate. The versatility of this new nitrogen protecting group is illustrated with a new synthesis of Selegiline, a monoamine oxidase-B inhibitor marketed for the treatment of Parkinson's disease. Easy on'easy off: The pymisyl group is introduced as a new protecting group for the activation of aziridines towards ring opening with organocuprates (see scheme). It is readily removed under very mild conditions with thiolates. The versatility of the approach is illustrated in a new synthesis of Selegiline, a drug marketed for the treatment of Parkinson's disease.
- Bornholdt, Jan,Felding, Jakob,Clausen, Rasmus P.,Kristensen, Jesper L.
-
supporting information; experimental part
p. 12474 - 12480
(2010/12/25)
-
- Synthesis of 2-Arylethylamines by the Curtius Rearrangement
-
2-Arylethylamine derivatives were synthesized using the Curtius reaction and with three different methods of preparing the acyl azide functional group. Carbamates derived from isocyanate were convenient protecting groups for alkylation of amines. Starting from benzaldehyde, amphetamine was prepared in three steps through an oxazolidin-2-one intermediate in 62% overall yield. Copyright Taylor & Francis Group, LLC.
- Schulze, Matthias
-
experimental part
p. 1461 - 1476
(2010/07/08)
-
- METHOD FOR MAKING PHARMACEUTICAL COMPOUNDS
-
A method of making a phenylethylamine of formula B: wherein R2, R3, R4, R5, R6, Rα, Rβ and Rn are each independently selected from hydrogen, alkyl, acyl, aryl, amido, amino acids, sugars and nucleotides. The method includes the reduction of a compound of formula A in the absence of base: wherein R2, R3, R4, R5, R6, Rα, Rβ and Rn are as defined above.
- -
-
Page/Page column 3
(2010/06/13)
-
- An efficient and general synthesis of primary amines by ruthenium-catalyzed amination of secondary alcohols with ammonia
-
Atom efficiency and selectivity are the key features of the first homogeneously catalyzed amination of secondary alcohols with ammonia to give the corresponding primary amines (see scheme). This novel amination method relies on the commercially available catalyst [Ru3(CO)12]/ cataCXium PCy and does not require any additional source of hydrogen.
- Imm, Sebastian,Neubert, Lorenz,Neumann, Helfried,Beller, Matthias
-
supporting information; experimental part
p. 8126 - 8129
(2011/02/22)
-
- δ13C and δ13H isotope ratios in amphetamine synthesized from benzaldehyde and nitroethane
-
Previous work in these laboratories and by Butzenlechner et al. and Culp et al. has demonstrated that the δ2H isotope value of industrial benzaldehyde produced by the catalytic oxidation of toluene is profoundly positive, usually in the range +300% to +500%. Synthetic routes leading to amphetamine, methylamphetamine or their precursors and commencing with such benzaldehyde may be expected to exhibit unusually positive δ2H values. Results are presented for δ13C and δ2H isotope values of 1-phenyl-2-nitropropene synthesized from an industrial source of benzaldehyde, having a positive δ2H isotope value, by a Knoevenagel condensation with nitroethane. Results are also presented for δ13C and δ2H isotope values for amphetamine prepared from the resulting 1-phenyl-2-nitropropene. The values obtained were compared with δ13C and δ2H isotope values obtained for an amphetamine sample prepared using a synthetic route that did not involve benzaldehyde. Finally, results are presented for samples of benzaldehyde, 1-phenyl-2-nitropropene and amphetamine that had been seized at a clandestine amphetamine laboratory.
- Collins, Michael,Salouros, Helen,Cawley, Adam T.,Robertson, James,Heagney, Aaron C.,Arenas-Queralt, Andrea
-
experimental part
p. 1653 - 1658
(2011/10/13)
-
- Synthesis and characterization of hydroxylated mesocarb metabolites for doping control
-
The synthesis and method of analysis of hydroxylated mesocarb metabolites are described. Six potential hydroxylated mesocarb metabolites were prepared, characterized, and compared with the mesocarb metabolites synthesized enzymatically in vitro using human liver proteins and also compared with metabolites extracted from human urine after oral administration of mesocarb. p-Hydroxymesocarb was the most prevalent metabolite (conjugated and non-conjugated) observed. With respect to doping analysis, synthesis of p-hydroxymesocarb, the main urinary metabolite of mesocarb, and its availability as a reference material is important.
- Vahermo, Mikko,Suominen, Tina,Leinonen, Antti,Yli-Kauhaluoma, Jari
-
experimental part
p. 201 - 209
(2009/05/09)
-
- Characterization of route specific impurities found in methamphetamine synthesized by the Leuckart and reductive amination methods
-
Impurity profiling of seized methamphetamine can provide very useful information in criminal investigations and, specifically, on drug trafficking routes, sources of supply, and relationships between seizures. Particularly important is the identification of "route specific" impurities or those which indicate the synthetic method used for manufacture in illicit laboratories. Previous researchers have suggested impurities which are characteristic of the Leuckart and reductive amination (Al/Hg) methods of preparation. However, to date and importantly, these two synthetic methods have not been compared in a single study utilizing methamphetamine hydrochloride synthesized in-house and, therefore, of known synthetic origin. Using the same starting material, 1-phenyl-2-propanone (P2P), 40 batches of methamphetamine hydrochloride were synthesized by the Leuckart and reductive amination methods (20 batches per method). Both basic and acidic impurities were extracted separately and analyzed by GC/MS. From this controlled study, two route specific impurities for the Leuckart method and one route specific impurity for the reductive amination method are reported. The intra- and inter-batch variation of these route specific impurities was assessed. Also, the variation of the "target impurities" recently recommended for methamphetamine profiling is discussed in relation to their variation within and between production batches synthesized using the Leuckart and reductive amination routes.
- Kunalan, Vanitha,Daeid, Niamh Nic,Kerr, William J.,Buchanan, Hilary A. S.,McPherson, Allan R.
-
experimental part
p. 7342 - 7348
(2010/04/06)
-
- Instantaneous SmI2/H2O/amine mediated reduction of nitroalkanes and α,β-unsaturated nitroalkenes
-
A rapid method for efficient reduction of nitroalkanes and α,β-unsaturated nitroalkenes using SmI2/H2O/amine has been developed.
- Ankner, Tobias,Hilmersson, G?ran
-
p. 5707 - 5710
(2008/02/10)
-
- Determination of the synthetic origin of methamphetamine samples by 2H NMR spectroscopy
-
Samples of methamphetamine, prepared according to the most common synthetic pathways, were submitted to natural-abundance 2H NMR spectroscopy. The deuterium content at the various sites of the molecule was found to depend on its synthetic history. The technique provides a chemical fingerprint of methamphetamine samples and can give hints to trace back the starting materials and the synthetic procedures.
- Armellin, Silvia,Brenna, Elisabetta,Frigoli, Samuele,Fronza, Giovanni,Fuganti, Claudio,Mussida, Daniele
-
p. 3113 - 3117
(2008/02/09)
-
- The facile preparation of primary and secondary amines via an improved Fukuyama-Mitsunobu procedure. Application to the synthesis of a lung-targeted gene delivery agent
-
An efficient modification of the Fukuyama-Mitsunobu procedure has been developed whereby primary or secondary amines can be synthesized from alkyl alcohols and the corresponding nosyl-protected/activated amine. Most importantly, the use of the DTBAD and diphenylpyridinylphosphine, as Mitsunobu reagents, generates reaction by-products that can be easily removed, providing a remarkably clean product mixture. This improved technique was implemented in the synthesis of a complex lipopeptide designed to target α 9β1-integrin proteins predominant on upper airway epithelial cells. The Royal Society of Chemistry 2005.
- Guisado, Cristina,Waterhouse, Jodie E.,Price, Wayne S.,Jorgensen, Michael R.,Miller, Andrew D.
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p. 1049 - 1057
(2007/10/03)
-
- From the production of amphetamine phenylpropanolamine
-
A process for making compound of formula Ifrom a phenylpropanolamine salt of formula IIwherein:R1 is hydrogen or a lower alkyl group;each R2 is independently a hydrogen, halogen, lower alkyl group, lower alkoxy groups, lower alkyl group substituted with 1 to 5 halogens, lower alkoxy groups substituted with 1 to 5 halogens, or both R2 together when on adjacent carbons constitute a -O(CH2)xO- where x is 1 to 4, thereby forming a ring structure fused with the phenyl group;R3 is a C1-C8-alkyl group, a C1-C12-aralkyl group, C1-C12-alkaryl group, or a phenyl group, each optionally substituted by 1 to 5 substituents selected from halogen, hydroxy, or C1-C6-alkyl; andHX is an equivalent of an organic or inorganic acid,the process comprising:(a) acylating the phenylpropanolamine salt of formula II with an acylating agent in a solvent at elevated temperature to make a reaction mixture containing an O-acylated phenylpropanolamine salt of formula III which can be isolated by the addition of a crystallization solvent, or optionally this mixture can be used in the next step; and(b) hydrogenating the O-acylated phenylpropanolamine salt to make the compound of formula I in the presence of a catalyst.
- -
-
Page/Page column 17-18
(2008/06/13)
-
- Catalytic N-sulfonyliminium ion-mediated cyclizations to α-vinyl-substituted isoquinolines and β-carbolines and applications in metathesis
-
Catalytic Sn(OTf)2-induced cyclization of linear, aryl-containing allylic N,O-acetals produced vinyl-substituted tetrahydroisoquinolines and tetrahydro-1H-β-carbolines. The usefulness of the vinyl moiety in the resulting products was demonstrated via the synthesis of various key building blocks for alkaloid structures. The α-vinyl moiety was utilized in a [2,3] sigmatropic rearrangement, in ring-closing metathesis and a cross-metathesis-based synthesis of vincantril, an antianoxia agent, and a synthetic member of the vincamine type natural products.
- Kinderman, Sape S.,Wekking, Monique M. T.,Van Maarseveen, Jan H.,Schoemaker, Hans E.,Hiemstra, Henk,Rutjes, Floris P. J. T.
-
p. 5519 - 5527
(2007/10/03)
-
- Free radical-mediated aryl amination and its use in a convergent [3 + 2] strategy for enantioselective indoline α-amino acid synthesis
-
The scope of aryl radical additions to the nitrogen of azomethines is described. Aryl, trifluoromethyl alkyl, and α,β-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%). α-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 α-amino acids with high ee. These new constrained phenyl alanine derivatives are now readily available for evaluation across a variety of applications.
- Viswanathan, Rajesh,Prabhakaran, Erode N.,Plotkin, Michael A.,Johnston, Jeffrey N.
-
p. 163 - 168
(2007/10/03)
-
- Low-valent Ruthenium Induced Simultaneous Reduction of Nitro Group and C-C Double Bond in Nitroolefin 1-Phenyl-2-nitropropene-1-
-
The reduction of 1-phenyl-2-nitropropene-1 (1) on using ruthenium complexes was studied in detail in order to correlate this method with those previously recorded in the literature for the hydrogenation of nitroolefins. A variety of products was isolated by varying the reaction temperature and solvent. Among them was 1-phenyl-2-propylamine (4), completely reduced from the selective both double bond and nitro group. 1-Phenyl-2-propanol (5) was observed due to reduction of phenylacetone at 125 deg C in the presence of ruthenium catalyst. When reaction temperature was lower than 125 deg C, by employing RuCl2(PPh3)3 complex, 1-phenyl-2-nitropropane (2) and phenylacetone (3) were obtained, respectively. Ru-BINAP complexes were attempted to produce chiral amine from starting material 1-phenyl-2-nitropropene-1 (1).
- Li, Yanjun,Izumi, Taeko
-
p. 505 - 508
(2007/10/03)
-
- CAL-B-catalyzed resolution of some pharmacologically interesting β-substituted isopropylamines
-
Some pharmacologically active amines such as amphetamine, the isomeric o-, m- and p-methoxyamphetamines, 4-phenylbutan-2-amine and mexiletine, as well as their corresponding acetamides, have been prepared in high yields and with very high enantiomeric excesses. The method consists of the Candida antarctica lipase B (CAL-B)-mediated enantioselective acetylation of racemic amines using ethyl acetate as solvent and acyl donor. The enzyme follows Kazlauskas' rule with all amines, (R)-amides being obtained as the major enantiomer in all cases. From the conversion values measured for both enantiomers, it can be deduced that the size of the substituents attached to the stereocenter is responsible for the enantioselectivity and rate of some of these reactions.
- Gonzalez-Sabin, Javier,Gotor, Vicente,Rebolledo, Francisca
-
p. 1315 - 1320
(2007/10/03)
-
- Stereoselectivity of cyclisations via N-acyliminium ions to form pyrido[2′,3′:3,4]pyrrolo[2,1-a]isoindole, -isoquinoline and -benz[c]azepine ring systems
-
Pyrido[2′,3′:3,4]pyrrolo[2,1-a]isoindole, -isoquinoline and -benz[c]azepine derivatives are obtained by heating in polyphosphoric acid (PPA) appropriate hydroxy lactam precursors derived from pyridine-2,3-dicarboximides. The stereoselectivity of ring closure is rationalised by considering the development of A(1,3) strain in the cyclisation step from N-acyliminium ion intermediates.
- Bahajaj,Vernon,Wilson
-
p. 1446 - 1451
(2007/10/03)
-
- Reduction of amphetamine hydroxylamine and other aliphatic hydroxylamines by benzamidoxime reductase and human liver microsomes
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For the reduction of N-hydroxylated derivatives of strongly basic functional groups, such as amidines, guanidines, and aminohydrazones, an oxygen-insensitive liver microsomal system, the benzamidoxime reductase, has been described. To reconstitute the complete activity of the benzamidoxime reductase, the system required cytochrome b5, NADH-cytochrome b5-reductase, and the benzamidoxime reductase, a cytochrome P450 enzyme, which has been purified to homogeneity from pig liver. It was not known if this enzyme system was also capable of reducing aliphatic hydroxylamines. The N-hydroxylation of aliphatic amines is a well-known metabolic process. It was of interest to study the possibility of benzamidoxime reductase reducing N-hydroxylated metabolites of aliphatic amines back to the parent compound. Overall, N-hydroxylation and reduction would constitute a futile metabolic cycle. As examples of medicinally relevant compounds, the hydroxylamines ofmethamphetamine, amphetamine, and N-methylamine as model compounds were investigated. Formation of methamphetamine and amphetamine was analyzed by newly developed HPLC methods. All three hydroxylamines were easily reduced by benzamidoxime reductase to their parent amines with reduction rates of 220.6 nmol min-1 (mg of protein)-1 for methamphetamine, 5.25 nmol min-1 (mg of protein)-1 for amphetamine, and 153 nmol min-1 (mg of protein)-1 for N-methylhydroxylamine. Administration of synthetic hydroxylamines of amphetamine and methamphetamine to primary rat neuronal cultures produced frank cell toxicity. Compared with amphetamine or the oxime of amphetamine, the hydroxylamines were significantly more toxic to primary neuronal cells. The benzamidoxime reductase is therefore involved in the detoxication of these reactive hydroxylamines.
- Clement,Behrens,Moller,Cashman
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p. 1037 - 1045
(2007/10/03)
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- An ammonia equivalent for the dimethyltitanocene-catalyzed intermolecular hydroamination of alkynes
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(Equation presented) Commercially available α-aminodiphenylmethane 1 (benzhydrylamine) serves as a convenient ammonia equivalent in the dimethyltitanocene-catalyzed intermolecular hydroamination of alkynes. The primary formed imines can be hydrogenated and cleaved directly to the corresponding primary amines by catalytic hydrogenation using Pd/C as catalyst.
- Haak, Edgar,Siebeneicher, Holger,Doye, Sven
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p. 1935 - 1937
(2007/10/03)
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- Polymer bound iminodicarbonate: A new ammonia equivalent for solid-phase synthesis of primary amines
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A polymer bound iminodicarbonate has been designed and its use in solid-phase synthesis of primary amines is reported. (C) Elsevier Science Ltd.
- Subramanyam
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p. 6537 - 6540
(2007/10/03)
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- A high-performance, tailor-made resolving agent: Remarkable enhancement of resolution ability by introducing a naphthyl group into the fundamental skeleton1
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A novel resolving agent, 2-naphthylglycolic acid (2-NGA), was designed for p-substituted 1-arylethylamines on the basis of the consideration that a rigid and large naphthyl group would be favorable for the close packing of supramolecular hydrogen-bond sheets formed between the carboxy groups of 2-NGA and the amino groups of p-substituted 1-arylethylamines. Racemic 2-NGA was readily available from commercially available raw materials, and both enantiopure forms could be obtained by simple diastereomeric resolution with enantiopure 1-phenyl-ethylamine. Thus-prepared enantiopure 2-NGA was found to have an excellent resolution ability not only for p-substituted 1-arylethylamines, but also for a wide variety of chiral primary amines. X-Ray crystallographic analyses of the less- and more-soluble diastereomeric salts revealed that this excellent resolution ability of 2-NGA arose from the formation of a supramolecular hydrogen-bond sheet with the primary amine, as we had expected, and also from the possible achievement of an infinite chain of CH... π interaction between its naphthyl group and the aromatic group of the amine, which was formed in the hydrophobic region of the supramolecular hydrogen-bond sheet.
- Kinbara, Kazushi,Harada, Yoshiko,Saigo, Kazuhiko
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p. 1339 - 1347
(2007/10/03)
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- A base-catalyzed domino-isomerization-hydroamination reaction - A new synthetic route to amphetamines
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An efficient synthesis of pharmaceutically interesting amphetamines by a base-catalyzed domino-isomerization- hydroamination reaction is presented. Starting from allylbenzene and various primary or secondary amines, the basic structural pattern of amphetamines is synthesized directly in yields of up to 91% in the presence of catalytic amounts of n-butyllithium. (C) 2000 Elsevier Science Ltd.
- Hartung, Christian G.,Breindl, Claudia,Tillack, Annegret,Beller, Matthias
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p. 5157 - 5162
(2007/10/03)
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- Convenient Access to Primary Amines by Employing the Barbier-Type Reaction of N-(Trimethylsilyl)imines Derived from Aromatic and Aliphatic Aldehydes
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A new versatile preparation of primary amines via benzylation of aromatic and aliphatic aldimines is described. Sonochemical and traditional methods for generation of the reactive intermediates are compared and contrasted. Competitive reactions were analyzed via free energy relationships to support the proposed alkylative mechanism.
- Gyenes, Ferenc,Bergmann, Kathryn E.,Welch, John T.
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p. 2824 - 2828
(2007/10/03)
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- Further studies of intramolecular motions in crystalline ammonium bromides by CP/MAS NMR
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A series of nine compounds consisting of dimethyl, trimethyl and ethyldimethyl ammonium bromides in which the other alkyl group contains a (2-phenyl)ethyl moiety were synthesised and studied by CP/MAS NMR. The results of dynamic NMR studies on the solids suggest that there is a dramatically wide range of molecular motions occurring in this simple series of compounds. A combination of dynamic line shape analyses and Τ1ρ measurements reveals the considerable extent of intramolecular group motions including rotations of trimethylammonium, ethyldimethylammonium and phenyl groups. Rates of rotation and activation parameters for these molecular motions are derived where appropriate.
- Riddell, Frank G.,Rogerson, Martin
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p. 249 - 255
(2007/10/03)
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- Preparation of secondary amines by reductive animation with metallic magnesium
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A novel and efficient method for the preparation of secondary amines by reductive animation of carbonyl compounds with primary amines has been developed. The reduction, effected with metallic magnesium in methanol, utilizing triethylamine-acetic acid as a buffer, gave pure secondary amines, mostly in good yields (65-80%). No formation of tertiary amines or alcohols was observed. Use of ammonium acetate as an amino component gave primary amines in modest yields (ca. 50%), together with variable amounts of secondary amines. Enamines failed to undergo reduction. The method is inexpensive, relatively rapid, operationally simple and suitable for large-scale preparations. In addition, a simple method for separation of primary amines from secondary ones has been developed.
- Micovic, Ivan V.,Ivanovic,Roglic, Goran M.,Kiricojevic, Vesna D.,Popovic, Jelena B.
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p. 265 - 269
(2007/10/03)
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- Asymmetric organic synthesis. Preparation and Birch reduction-alkylation of 2-methyl-3,4-dihydroisoquinolin-1-ones
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Birch reductions of 2-methyl-3,4-dihydroisoquinolin-1-ones 1 and 6 generate enolates 2a and 2b and alkylations provide 1,4-cyclohexadienes 3a-3e and 7a-7c. The synthesis of a racemic structural analogue, 9, of the potent analgetic levorphanol is described.
- Schultz, Arthur G.,Kirincich, Steven J.,Rahm, Rainer
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p. 4551 - 4554
(2007/10/02)
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- Enantiomer separation via diastereoisomeric salt formation and liquid-liquid phase transition
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On reacting racemic amine bases with half equivalent amount of sodium-hydrogen-tartrate in a water-benzene solvent system, the mixed-neutral tartrate accumulates in the aqueous phase, while the free base concentrates in the organic phase, resulting in enantiomer separation without crystallization.
- Acs, Maria,Kozma, David,Fogassy, Elemer
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p. 475 - 478
(2007/10/02)
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- Phenethylthiazolethiourea (PETT) compounds, a new class of HIV-1 reverse transcriptase inhibitors. 1. Synthesis and basic structure-activity relationship studies of PETT analogs
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A novel series of potent specific HIV-1 inhibitory compounds is described. The lead compound in the series, N-(2-phenethyl)-N'-(2-thiazolyl)thiourea (1), inhibits HIV-1 RT using rCdG as the template with an IC50 of 0.9 μM. In MT-4 cells, compound 1 inhibits HIV-1 with an ED50 of 1.3 μM. The 50% cytotoxic dose in cell culture is >380 μM. The chemical structure-activity relationship (SAR) was developed by notionally dividing the lead compound in four quadrants. The SAR strategy had two phases. The first phase involved optimization of antiviral activity through independent variation of quadrants 1-4. The second phase involved the preparation of hybrid structures combining the best of these substituents. Further SAR studies and pharmacokinetic considerations led to the identification of N-(2-pyridyl)-N'-(5-bromo-2- pyridyl)-thiourea (62; LY300046 · HCl) as a candidate for clinical evaluation. LY300046 · HCl inhibits HIV-1 RT with an IC50 of 15 nM and in cell culture has an ED50 of 20 nM.
- Bell,Cantrell,Hogberg,Jaskunas,Johansson,Jordan,Kinnick,Lind,Morin Jr.,Noreen,Oberg,Palkowitz,Parrish,Pranc,Sahlberg,Ternansky,Vasileff,Vrang,West,et al.
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p. 4929 - 4936
(2007/10/03)
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- Immunoreagents
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An immunofluorescent assay method, characterized in using an immunodetective reagent, which is an antigen-like substance comprising a fluorescent substance and an antigen chemically bonded thereto with or without intervention of an additional chemical bond, said fluorescent substance being changed in the wavelength or intensity of the fluorescence when an antibody comes close thereto, and said antigen being specific to said antibody.
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- Binding of Phenylalkylamine Derivatives at 5-HT1C and 5-HT2 Serotonin Receptors: Evidence for a Lack of Selectivity
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Certain phenyalkylamine derivatives have been considered to bind selectively at 5-HT2 serotonin receptors.It is now recognized that the most widely used derivatives, i.e., 1-(2,5-dimethoxy-4-X-phenyl)-2-aminopropanes where X = Me (DOM), Br (DOB), and I (DOI) (1-3, respectively) also bind at the more recently identified population of serotonin 5-HT1C receptors.The purpose of the present investigation was to determine whether simple phenylalkylamines bind selectively at one population of receptors over the other.An examination of 34 derivatives reveals (i) similar structure-affinity relationships and (ii) a significant correlation (r = >0.9, n = 25) between 5-HT1C and 5-HT2 affinity.None of the compounds included in the present study displayed more than a 10-fold selectivity for one population of these receptors over the other; the results suggest that these compounds (including the widely used 5-HT2 agonists DOB and DOI) are 5-HT1C/5-HT2 agents.
- Glennon, Richard A.,Raghupathi, Reva,Bartyzel, Piotr,Teitler, Milt,Leonhardt, Sigrun
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p. 734 - 740
(2007/10/02)
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