- Synthesis of optically active 2-aminotetraline derivatives via enantioselective ruthenium-catalyzed hydrogenation of ene carbamates
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The enantioselective hydrogenation of prochiral ene carbamates, directly derived from 2-tetralone, was completed using a catalytic ruthenium system generated from Ru(COD)(methallyl)2, an optically pure diphosphine and a strong acid containing a non-coordinating counter anion.
- Dupau, Philippe,Hay, Anne-Emmanuelle,Bruneau, Christian,Dixneuf, Pierre H.
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Read Online
- Stereoselective Synthesis of Protected Amines and Diamines from Alkenes using N,N-Dichloro-t-butylcarbamate
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N,N-Dichloro-t-butylcarbamate (1) reacts with alkenes (2) in a regio- and stereo-selective manner to give the trans-chlorocarbamate adducts (3).Treatment of (3) with base gives aziridines (5), and reaction of (3) and (5) with sodium azide leads selectively to the versatile diamine precursors (6) and (7).In situ reduction of (3) with Zn/NH4OAc leads directly to Boc-protected amines (10).
- Orlek, Barry S.,Stemp, Geoffrey
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Read Online
- ION CHANNEL INHIBITOR COMPOUNDS FOR CANCER TREATMENT
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The present invention concerns a compound of following general formula (I): where: either R is an R1 group and R′ is an -A1-Cy1 group, or R is an -A1-Cy1 group and R′ is an R1 group, R1 particularly being H or (C1-C6)alkyl group;A1 being an —NH— radical or —NH—CH2— radical;Cy1 particularly being a phenyl group,A is a fused (hetero)aromatic ring having 5 to 7 atoms, for use for treating cancer.
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Paragraph 0261; 0262; 0263; 0292; 0293
(2021/01/25)
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- Direct reductive amination of ketones with ammonium salt catalysed by Cp*Ir(iii) complexes bearing an amidato ligand
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A series of half-sandwich Ir(iii) complexes1-6bearing an amidato bidentate ligand were conveniently synthesized and applied to the catalytic Leuckart-Wallach reaction to produce racemic α-chiral primary amines. With 0.1 mol% of complex1, a broad range of ketones, including aryl ketones, dialkyl ketones, cyclic ketones, α-keto acids, α-keto esters and diketones, could be transformed to their corresponding primary amines with moderate to excellent yields (40%-95%). Asymmetric transformation was also attempted with chiral Ir complexes3-6, and 16% ee of the desired primary amine was obtained. Despite the unsatisfactory enantio-control achieved so far, the current exploration might stimulate more efforts towards the discovery of better chiral catalysts for this challenging but important transformation.
- Dai, Zengjin,Pan, Ying-Min,Wang, Shou-Guo,Yin, Qin,Zhang, Xumu
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supporting information
p. 8934 - 8939
(2021/11/04)
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- Direct Access to Primary Amines from Alkenes by Selective Metal-Free Hydroamination
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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
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supporting information
p. 9875 - 9880
(2021/03/29)
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- Amine Transaminase from Exophiala Xenobiotica - Crystal Structure and Engineering of a Fold IV Transaminase that Naturally Converts Biaryl Ketones
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Amine transaminases are frequently used for the production of chiral amines starting from prochiral ketones. These amines can be applied as active pharmaceutical ingredients or drug precursors. However, there are still limitations to the use of amine transaminases when it comes to bulky ketone substrates, such as biaryl ketones. Using data mining, an (R)-selective amine transaminase from Exophiala xenobiotica was identified which naturally converts biaryl ketone substrates to the corresponding amines with up to 85% conversion and excellent enantioselectivity (>99% ee). Its protein crystal structure was obtained with a resolution of 1.52 ?, which enabled us to explain this interesting substrate acceptance. Structure-guided protein engineering resulted in a quintuple variant with increased stability. Moreover, the amino acid exchange T273S increased the activity and broadened the substrate scope, enabling conversions of various biaryl ketones with up to >99%. A preparative biotransformation of 1-(4-(pyridin-3-yl)phenyl)ethenone at 75 mM (15 g/L) resulted in 96% of isolated yield of the respective amine.
- Telzerow, Aline,Paris, Juraj,H?kansson, Maria,González-Sabín, Javier,Ríos-Lombardía, Nicolás,Schürmann, Martin,Gr?ger, Harald,Morís, Francisco,Kourist, Robert,Schwab, Helmut,Steiner, Kerstin
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p. 1140 - 1148
(2019/01/21)
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- N-Alkylation of Aqueous Ammonia with Alcohols Leading to Primary Amines Catalyzed by Water-Soluble N-Heterocyclic Carbene Complexes of Iridium
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A new catalytic system for the N-monoalkylation of aqueous ammonia with a variety of alcohols was developed. Water-soluble dicationic complexes of iridium bearing N-heterocyclic carbene and diammine ligands exhibited high catalytic activity for this type of reaction on the basis of hydrogen-transfer processes without generating harmful or wasteful byproducts. Various primary amines were efficiently synthesized by using safe, inexpensive, and easily handled aqueous ammonia as a nitrogen source. For example, the reaction of 1-(4-methylphenyl)ethanol with aqueous ammonia in the presence of a water-soluble N-heterocyclic carbene complex of iridium at 150 °C for 40 h gave 1-(4-methylphenyl)ethylamine in 83 % yield.
- Fujita, Ken-Ichi,Furukawa, Shohichi,Morishima, Namino,Shimizu, Mineyuki,Yamaguchi, Ryohei
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p. 1993 - 1997
(2018/03/13)
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- (R)- SELECTIVE AMINATION
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The present invention relates to a method for the enzymatic synthesis of enantiomerically enriched (R)-amines of general formula [1][c] from the corresponding ketones of the general formula [1][a] by using novel transaminases. These novel transaminases are selected from two different groups: either from a group of some 20 proteins with sequences as specified herein, or from a group of proteins having transaminase activity and isolated from a microorganism selected from the group of organisms consisting of Rahnella aquatilis, Ochrobactrum anthropi, Ochrobactrum tritici, Sinorhizobium morelense, Curtobacterium pusiffium, Paecilomyces lilacinus, Microbacterium ginsengisoli, Microbacterium trichothecenolyticum, Pseudomonas citronellolis, Yersinia kristensenii, Achromobacter spanius, Achromobacter insolitus, Mycobacterium fortuitum, Mycobacterium frederiksbergense, Mycobacterium sacrum, Mycobacterium fluoranthenivorans, Burkhoideria sp., Burkhoideria tropica, Cosmospora episphaeria, and Fusarium oxysporum.
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Paragraph 0120; 0121; 0122
(2016/03/22)
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- CATALYST COMPOUNDS
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The present invention relates to an iridium-based catalyst compound for hydrogenating reducible moieties, especially imines and iminiums, the catalyst compounds being defined by the formulas: where ring B is either itself polycyclic, or ring B together with R is polycyclic. The catalysts of the invention are particularly effective in reductive amination procedures 10 which involve the in situ generation of the imine or iminium under reductive hydrogenative conditions.
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Paragraph 0314; 0322
(2015/03/28)
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- Primary amines by transfer hydrogenative reductive amination of ketones by using cyclometalated IrIII catalysts
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Cyclometalated iridium complexes are found to be versatile catalysts for the direct reductive amination (DRA) of carbonyls to give primary amines under transfer-hydrogenation conditions with ammonium formate as both the nitrogen and hydrogen source. These complexes are easy to synthesise and their ligands can be easily tuned. The activity and chemoselectivity of the catalyst towards primary amines is excellent, with a substrate to catalyst ratio (S/C) of 1000 being feasible. Both aromatic and aliphatic primary amines were obtained in high yields. Moreover, a first example of homogeneously catalysed transfer-hydrogenative DRA has been realised for β-keto ethers, leading to the corresponding β-amino ethers. In addition, non-natural α-amino acids could also be obtained in excellent yields with this method. Reduce the work! A broad range of ketones have been successfully aminated to afford primary amines under transfer-hydrogenation conditions by using ammonium formate as the amine source and 0.1 mol % of a cyclometalated IrIII catalyst (see scheme). Copyright
- Talwar, Dinesh,Salguero, Noemi Poyatos,Robertson, Craig M.,Xiao, Jianliang
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supporting information
p. 245 - 252
(2014/01/17)
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- POTENT SMALL MOLECULE INHIBITORS OF AUTOPHAGY, AND METHODS OF USE THEREOF
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Certain aspects of the invention relate to small molecule autophagy inhibitors, and their use for treatment and prevention of cancers and acute pancreatitis. Medicinal chemistry studies led to small molecular autophagy inhibitors with improved potency and selectivity.
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Page/Page column 56
(2014/09/29)
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- A novel chimeric amine dehydrogenase shows altered substrate specificity compared to its parent enzymes
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We created a novel chimeric amine dehydrogenase (AmDH) via domain shuffling of two parent AmDHs ('L- and F-AmDH'), which in turn had been generated from leucine and phenylalanine DH, respectively. Unlike the parent proteins, the chimeric AmDH ('cFL-AmDH') catalyzes the amination of acetophenone to (R)-methylbenzylamine and adamantylmethylketone to adamantylethylamine.
- Bommarius, Bettina R.,Schürmann, Martin,Bommarius, Andreas S.
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p. 14953 - 14955
(2015/02/19)
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- CATALYST COMPOUNDS
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The present invention relates to an iridium-based catalyst compound for hydrogenating reducible moieties, especially imines and iminiums, the catalyst compounds being defined by the formulas: where ring B is either itself polycyclic, or ring B together with R is polycyclic. The catalysts of the invention are particularly effective in reductive amination procedures 10 which involve the in situ generation of the imine or iminium under reductive hydrogenative conditions.
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Paragraph 00163; 00171
(2013/11/05)
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- Quenched skeletal Ni as the effective catalyst for selective partial hydrogenation of polycyclic aromatic hydrocarbons
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Quenched skeletal Ni is an active and selective catalyst for selective partial hydrogenation of polycyclic aromatic hydrocarbons (PAHs). The molecular structure of PAHs significantly dominate the hydrogenation process and furthermore, the distribution of hydrogenated products.
- Liu, Chengyun,Rong, Zeming,Sun, Zhuohua,Wang, Yong,Du, Wenqiang,Wang, Yue,Lu, Lianhai
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p. 23984 - 23988
(2013/11/19)
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- Asymmetric amination of tetralone and chromanone derivatives employing ω-transaminases
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Various (S)-selective and (R)-selective ω-transaminases were investigated for the amination of 1- and 2-tetralone and derivatives as well as of 3- and 4-chromanone. All ketones tested were aminated to give the corresponding enantiopure amines (ee > 99%) employing at least one of the enzymes investigated. In most of the cases the (S)- as well as the (R)-enantiomer was obtained in optically pure form. The amination of 3-chromanone was performed on a 100 mg scale leading to optically pure (R)-3-aminochromane (ee > 99%) with complete conversion and 78% isolated yield.
- Pressnitz, Desiree,Fuchs, Christine S.,Sattler, Johann H.,Knaus, Tanja,Macheroux, Peter,Mutti, Francesco G.,Kroutil, Wolfgang
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p. 555 - 559
(2013/06/05)
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- Investigation of one-enzyme systems in the ω-transaminase-catalyzed synthesis of chiral amines
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ω-Transaminase (TA) catalyzed asymmetric syntheses of amines were carried out in the one enzyme systems with wild-type enzymes (S)-TA from Pseudomonas aeruginosa, (S)-TA from Paracoccus denitrificans and (R)-TA from Aspergillus terreus. The scope of amine donors and aromatic carbonyl substrates was thoroughly explored. Among the range of potential amino donors, 2-propylamine, 2-butylamine and 1-phenylethylamine were found as promising candidates, which gave superior conversions in the amination reactions compared to other donors. Various prochiral aromatic ketones were accepted as substrates by the investigated enzymes. In most cases, good to excellent conversions (up to 98%) to the amine products with excellent e.e.-values (>99.9% for (S) or (R)) were obtained by the action of a single enzyme and an appropriate amino donor. (S)-TA from Paracoccus denitrificans was found to accept bulky ketones, e.g. 1-indanone, α- and β-tetralone or 2-acetonaphthone, in the asymmetric amination. In some cases the enantiomeric excesses in the amination reactions were dependent on the amino donor. More-over, the influence of the pH, temperature and cosolvents on the outcome of reactions was additionally investigated.
- Fesko, Kateryna,Steiner, Kerstin,Breinbauer, Rolf,Schwab, Helmut,Schuermann, Martin,Strohmeier, Gernot A.
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p. 103 - 110
(2013/10/22)
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- Artificial multi-enzyme networks for the asymmetric amination of sec-alcohols
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Various artificial network designs that involve biocatalysts were tested for the asymmetric amination of sec-alcohols to the corresponding α-chiral primary amines. The artificial systems tested involved three to five redox enzymes and were exemplary of a range of different sec-alcohol substrates. Alcohols were oxidised to the corresponding ketone by an alcohol dehydrogenase. The ketones were subsequently aminated by employing a ω-transaminase. Of special interest were redox-neutral designs in which the hydride abstracted in the oxidation step was reused in the amination step of the cascade. Under optimised conditions up to 91 % conversion of an alcohol to the amine was achieved. Trickle-down effect: The asymmetric amination of sec-alcohols to the corresponding α-chiral primary amines was performed with a biocatalytic cascade whereby the various steps were interconnected through the cofactors/cosubstrates. In a redox-neutral cascade and under optimised conditions, up to 91 % conversion of an alcohol to the amine was achieved. Copyright
- Tauber, Katharina,Fuchs, Michael,Sattler, Johann H.,Pitzer, Julia,Pressnitz, Desiree,Koszelewski, Dominik,Faber, Kurt,Pfeffer, Jan,Haas, Thomas,Kroutil, Wolfgang
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p. 4030 - 4035
(2013/04/10)
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- N-octanoyldimethylglycine trifluoroethyl ester, an acyl donor leading to highly enantioselective protease-catalysed kinetic resolution of amines
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The use of N-octanoyldimethylglycine trifluoroethyl ester as acyl donor in the kinetic resolution of aliphatic amines catalysed by proteases led to enantiomeric ratios >200 in most cases. The resolutions mediated by Protex 6L were shown to be much faster
- Queyroy, Severine,Vanthuyne, Nicolas,Gastaldi, Stephane,Bertrand, Michele P.,Gil, Gerard
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supporting information; experimental part
p. 1759 - 1764
(2012/08/08)
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- Reductive amination of ketones: Novel one-step transfer hydrogenations in batch and continuous-flow mode
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Various ketones were efficiently transformed into the corresponding amines using ammonium formate in the presence of Zn dust or 10% Pd/C. The low-cost Zn dust method proved to be effective in amine formation from carbonyl groups at the benzylic side-chain position of aromatic systems, whereas 10% Pd/C was an efficient catalyst in the reductive aminations of carbonyl groups non-conjugated with any π-system. The 10% Pd/C-catalyzed reductions were performed more effectively in a continuous-flow X-Cube reactor than in the batch system.
- Falus, Péter,Boros, Zoltán,Hornyánszky, Gábor,Nagy, József,Darvas, Ferenc,ürge, László,Poppe, László
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supporting information; experimental part
p. 1310 - 1312
(2011/03/22)
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- Chemoenzymatic dynamic kinetic resolution of primary amines catalyzed by CAL-B at 38-40°c
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The (R)-selective chemoenzymatic dynamic kinetic resolution of primary amines was performed at 38-40 °C in MTBE, in good to high yields and with high enantiomeric excesses. These reactions associating CAL-B to octanethiol as radical racemizing agent were carried out in the presence of methyl β-methoxy propanoate as acyl donor, under photochemical irradiation at 350 nm in glassware.
- Poulhes, Florent,Vanthuyne, Nicolas,Bertrand, Michele P.,Gastaldi, Stephane,Gil, Gerard
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experimental part
p. 7281 - 7286
(2011/10/10)
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- Synthesis and evaluation of dimeric 1,2,3,4-Tetrahydro-naphthalenylamine and Indan-1-ylamine derivatives with mast cell-stabilising and anti-allergic activity
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In a continuation of our studies into 4-Amino-3,4-dihydro-2H-naphthalen-1-ones as novel modulators of allergic and inflammatory phenomena, we have extended our work to include dimeric analogues. Of these derivatives, the most promising activity was seen with tertiary amine 58a, which exhibited potent mast cell-stabilising activity in vitro against a variety of stimuli and also in vivo against passive cutaneous anaphylaxis.
- Barlow, James W.,Walsh, John J.
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experimental part
p. 25 - 37
(2010/03/04)
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- Asymmetric catalytic aziridination of dihydronaphthalenes for the preparation of substituted 2-aminotetralins
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An enantioselective synthesis of substituted 2-aminotetralins from dihydronaphthalenes in four steps is described. The key step is the Jacobsen's (diimine)copper-catalyzed asymmetric aziridination of dihydronaphthalenes to the respective aziridines in 33-82% yields and 60-87% enantiomeric excess. The enantioselectivity and the yield were dependent on the properties of the nitrene precursor. pTsNIPh appeared in general to give better results than pNsNIPh. Aziridines were ring-opened in the benzylic position by catalytic hydrogenolysis in quantitative yields, and deprotected in two steps to the respective 2-aminotetralins in 66-85% yields. The synthesis of (S)-2-aminotetralin (>98% ee) and (S)-2-amino-7-methoxytetralin (56% ee) were accomplished in 30 and 52% overall yields, respectively.
- Aaseng, Jon Erik,Melnes, Silje,Reian, Gard,Gautun, Odd R.
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experimental part
p. 9790 - 9797
(2011/02/22)
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- Indirect and direct catalytic asymmetric reductive amination of 2-tetralone
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Herein we report a one-pot catalytic asymmetric reductive amination of 2-tetralone. High-throughput screening of a small library of chiral ligands allowed us to perform the enantioselective hydrogenation of the intermediate enamine with up to 60% ee and a one-pot reaction with up to 47% enantiomeric excess of the desired amine.
- Bondarev, Oleg,Bruneau, Christian
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experimental part
p. 1350 - 1354
(2010/10/21)
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- SUBSTITUTED FLUOROETHYL UREAS AS ALPHA 2 ADRENERGIC AGENTS
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Therapeutic compounds, and methods, compositions, and medicaments related thereto are disclosed herein.
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Page/Page column 40
(2008/12/04)
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- Synthesis and structure activity relationships of novel non-peptidic metallo-aminopeptidase inhibitors
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Racemic derivatives of 3-amino-2-tetralone were synthesised and evaluated for their ability to inhibit metallo-aminopeptidase activities. New compounds substituted in position 2 by methyl ketone, substituted oximes or hydroxamic acids as well as heterocyclic derivatives were evaluated against representative members of zinc-dependent aminopeptidases: leucine aminopeptidase (E.C. 3.4.11.1), aminopeptidase-N (E.C. 3.4.11.2), Aeromonas proteolytica aminopeptidase (E.C. 3.4.11.10), and the aminopeptidase activity of leukotriene A4 hydrolase (E.C. 3.3.2.6). Several compounds showed Ki values in the low micromolar range against the 'one-zinc' aminopeptidases, while most of them were rather poor inhibitors of the 'two-zinc' enzymes. This interesting selectivity profile may guide the design of new, specific inhibitors of target mammalian aminopeptidases with one active site zinc.
- Albrecht, Sebastien,Defoin, Albert,Salomon, Emmanuel,Tarnus, Celine,Wetterholm, Anders,Haeggstroem, Jasper Z.
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p. 7241 - 7257
(2007/10/03)
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- Redox-photosensitized aminations of 1,2-benzo-1,3-cycloalkadienes, arylcyclopropanes, and quadricyclane with ammonia
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1,2,4-Triphenylbenzene and 2,2′-methylenedioxy-1,1′ -binaphthalene successfully photosensitized the aminations of 1,2-benzo-1,3-cycloalkadienes, arylcyclopropanes, and quadricyclane with ammonia and primary amines in the presence of m- or p-dicyanobenzene, which gave the 4-amino-1,2-benzocycloalkenes, 3-amino-1-arylpropanes, and 7-amino-5-(p-cyanophenyl)bicyclo[2.2.1]hept-2-ene, respectively. A key pathway for the photosensitized amination is the hole transfer from the cation radicals of the sensitizers that were generated by photoinduced electron transfer to the electron acceptors to the substrates. Therefore, it was found that the relationships in oxidation potentials between the sensitizers and the substrates and the positive charge distribution of the cation radicals of the substrates were important factors for the efficient amination.
- Yasuda, Masahide,Kojima, Ryuji,Tsutsui, Hiroshi,Utsunomiya, Daigo,Ishii, Kazuaki,Jinnouchi, Koutaro,Shiragami, Tsutomu
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p. 7618 - 7624
(2007/10/03)
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- A chemoenzymatic synthesis of (2R)-8-substituted-2-aminotetralins
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(2R)-2-Amino-8-methoxy-1,2,3,4-tetrahydronaphthalene, a useful precursor of the 5-hydroxytryptamine receptor agonist 8-OH-DPAT ((2R)-2-(dipropylamino)-8-hydroxytetrahydronaphthalene), has been synthesized from 1-methoxynaphthalene through a chemoenzymatic protocol. The same protocol has been subsequently applied to the synthesis of other (2R)-2-amino-1,2,3,4-tetrahydronaphthalenes.
- Orsini, Fulvia,Sello, Guido,Travaini, Elena,Di Gennaro, Patrizia
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p. 253 - 259
(2007/10/03)
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- A novel asymmetric route to 2-amino-1,2,3,4-tetrahydronaphthalenes
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A novel asymmetric route to 2-amino-1,2,3,4-tetrahydronaphthalenes has been demonstrated starting from phthalimidovinylglycinol (PVG). Functionalisation of PVG via Heck reaction, olefin hydrogenation and cyclisation provides the title products. (C) 2000 Elsevier Science Ltd.
- Harris, Michael C. J.,Jackson, Mark,Lennon, Ian C.,Ramsden, James A.,Samuel, Helen
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p. 3187 - 3191
(2007/10/03)
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- Synthesis, evaluation, and comparative molecular field analysis of 1- phenyl-3-amino-1,2,3,4-tetrahydronaphthalenes as ligands for histamine H1 receptors
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A series of 1-phenyl-3-amino-1,2,3,4-tetrahydronaphthalenes (1-phenyl- 3-aminotetralins, PATs) previously was found to modulate tyrosine hydroxylase activity and dopamine synthesis in rodent forebrain through interaction with a binding site labeled by [3H]-(-)-(1R,3S)-trans-H2-PAT. Recently, we have discovered that PATs also bind with high affinity to the [3H]mepyramine- labeled H1 receptor in rat and guinea pig brain. Here, we report the synthesis and biological evaluation of additional PAT analogues in order to identify differences in binding at these two sites. Further molecular modifications involve the pendant phenyl ring as well as quaternary amine compounds. Comparison of about 38 PAT analogues, 10 structurally diverse H1 ligands, and several other CNS-active compounds revealed no significant differences in affinity at [3H]-(-)-trans-H2-PAT sites versus [3H]mepyramine-labeled H1 receptors. These results, together with previous autoradiographic brain receptor-mapping studies that indicate similar distribution of [3H]-(-)-trans-H2-PAT sites and [3H]mepyramine-labeled H1 receptors, suggest that both radioligands label the same histamine H1 receptors in rodent brain. We also report a revision of our previous comparative molecular field analysis (CoMFA) study of the PAT ligands that yields a highly predictive model for 66 compounds with a cross-validated R2 (q2) value of 0.67. This model will be useful for the prediction of high- affinity ligands at radiolabeled H1 receptors in mammalian brain.
- Bucholtz, Ehren C.,Brown, Randal L.,Tropsha, Alexander,Booth, Raymond G.,Wyrick, Steven D.
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p. 3041 - 3054
(2007/10/03)
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- Catalytic asymmetric hydroboration-amination
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A one-pot asymmetric synthesis of primary amines from vinylarenes via catalytic hydroboration is described.
- Fernandez, Elena,Hooper, Mark W.,Knight, Frances I.,Brown, John M.
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p. 173 - 174
(2007/10/03)
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- Asymmetric synthesis of β-aminotetralins by electrophilic amination
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An effective synthesis of β-aminotetralins (6) including an asymmetric electrophlic amination by di-t-butyl azodicarboxylate is reported. Depending on the chiral auxiliaries (S)-7a-d, the central intermediates 9 and 10 could be isolated in 62-80% de. Subsequent hydrolysis and reductive degradation resulted in the nonracemic final products 6 (57-84% ee). Separation of the diastereomeric intermediates by chromatography makes possible the synthesis of optically pure products. An induction model for the asymmetric amination is provided.
- Gmeiner, Peter,Bollinger, Bernd
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p. 10909 - 10922
(2007/10/02)
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- AMINO ACID DERIVATIVES CYCLIZED AT THE C-TERMINAL
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Novel α-substituted Trp dipeptoid derivatives cyclized at the C-terminal useful as agents in the treatment of obesity, hypersecretion of gastric acid in the gut, gastrin-dependent tumors, or as antipsychotics are disclosed. Further, the compounds are antianxiety agents and antiulcer agents. They are agents useful for preventing the response to the withdrawal from chronic treatment with or use of nicotine, diazepam, alcohol, cocaine, caffeine, or opioids. The compounds of the invention are also useful in treating and/or preventing panic attacks. Also disclosed are pharmaceutical compositions and methods of treatment using the compounds as well as processes for preparing them and novel intermediates useful in their preparation. An additional feature of the invention is the use of the compounds in diagnostic compositions.
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- Aryloxypropanolaminotetralins, a process for their preparation and pharmaceutical compositions containing them
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Aryloxypropanolaminotetralins with beta-antagonist activity of the formula STR1 wherein R is hydrogen, hydroxy or methoxy and Ar is an optionally substituted aromatic or heteroaromatic group, in optically active or inactive form as well as their acid addition salts are described.A process for their preparation and pharmaceutical compositions containing the compounds of formula (i) or their pharmaceutically acceptable acid addition salts, are also described.
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- Efficient Methodology for the Preparation of β-Aminotetralin Derivatives via Electrophilic Amination
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A mild and efficient method for the construction of β-aryl amines from the corresponding α-aryl ketones is presented.The key step of the synthesis involve an electrophilic amination by dibenzyl azodicarboxylate followed by a stereoselective LiHBEt3 reduction.The reaction sequence is applied to the synthesis of the tricyclic ergoline analogue 4. Key words: electrophilic amination; stereoselective reduction; α-amino ketones.
- Gmeiner, Peter,Bollinger, Bernd
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p. 5927 - 5930
(2007/10/02)
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- Asymmetric Synthesis Using Chirally Modified Borohydrides. Part 3. Enantioselective Reduction of Ketones and Oxime Ethers with Reagents Prepared from Borane and Chiral Amino Alcohols
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The asymmetric reduction of aromatic and aliphatic ketones, halogeno ketones, keto esters, and ketone oxime ethers with reagents prepared from borane and chiral amino alcohols has been investigated.When α,α-diphenyl-β-amino alcohols, such as (2S,3R)-(-)-2-amino-3-methyl-1,1-diphenylpentanol (2d), were used as a chiral auxiliary, very high enantioselectivities (ca. 90percent e.e.) were obtained in the reduction of various ketones and oxime ethers.
- Itsuno, Shinichi,Nakano, Michio,Miyazaki, Koji,Masuda, Hirofumi,Ito, Koichi,et al.
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p. 2039 - 2044
(2007/10/02)
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