- Versatile Dynamic Covalent Assemblies for Probing π-Stacking and Chirality Induction from Homotopic Faces
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Herein we report for the first time the use of dynamic covalent reactions (DCRs) for building a π-stacking model system and further quantifying its substituent effects (SEs), which remain a topic of debate despite the rich history of stacking. A general DCR between 10-methylacridinium ion and primary amines was discovered, in which π-stacking played a stabilizing role. Facile quantification of SEs with in situ competing π-stacking systems was next achieved in the form of amine exchange exhibiting structural diversity by simply varying components. The linear correlation with σm in Hammett plots indicates the dominance of purely electrostatic SEs, and the additivity of SEs is in line with the direct interaction model. With α-chiral amines π-stacking within the adduct enabled chirality transfer from homotopic faces. The strategy of dynamic covalent assembly should be appealing to future research of probing weak interactions and manipulating chirality.
- Ye, Hebo,Hai, Yu,Ren, Yulong,You, Lei
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supporting information
p. 3804 - 3809
(2017/03/27)
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- Bioinspired organocatalytic aerobic C-H oxidation of amines with an ortho -quinone catalyst
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A simple bioinspired ortho-quinone catalyst for the aerobic oxidative dehydrogenation of amines to imines is reported. Without any metal cocatalysts, the identified optimal ortho-quinone catalyst enables the oxidations of α-branched primary amines and cyclic secondary amines. Mechanistic studies have disclosed the origins of different performances of ortho-quinone vs para-quinone in biomimetic amine oxidations.
- Qin, Yan,Zhang, Long,Lv, Jian,Luo, Sanzhong,Cheng, Jin-Pei
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supporting information
p. 1469 - 1472
(2015/03/30)
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- A Single Lipase-Catalysed One-Pot Protocol Combining Aminolysis Resolution and Aza-Michael Addition: An Easy and Efficient Way to Synthesise β-Amino Acid Esters
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A novel one-pot protocol combining aza-Michael addition and aminolysis resolution was developed to obtain chiral β-amino acid esters with lipase B from Candida antarctica (CAL-B) as the only catalyst. This method is conducted under mild reaction conditions and is very easy to handle. After a series of detailed optimization studies, ten racemic aromatic or aliphatic amines were subjected to this one-pot procedure, and twelve chiral β-amino acid esters and ten chiral amides were successfully synthesised with excellent ee values in theoretical yields. Scaled-up procedures also worked without apparent reduction in reaction rate or enantioselectivity, which makes this method suitable for large-scale production of chiral β-amino acid esters. A one-pot protocol for simultaneous synthesis of chiral β-amino acid esters and amides was developed by combining single lipase B from Candida antarctica (CAL-B) catalysed aza-Michael addition and aminolysis resolution. This method requires mild reaction conditions and is very easy to handle. Chiral β-amino acid esters and chiral amides were obtained with excellent ee values and in theoretical yields.
- Xu, Fan,Wu, Qiongsi,Chen, Xiaoyang,Lin, Xianfu,Wu, Qi
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supporting information
p. 5393 - 5401
(2015/08/24)
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- Liquid chromatographic resolution of fendiline and its analogues on a chiral stationary phase based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid
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Fendiline, an effective anti-anginal drug for the treatment of coronary heart diseases, and its sixteen analogues were resolved on a CSP based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid. Fendiline was resolved quite well with the separation factor (α) of 1.25 and resolution (RS ) of 1.55 when a mobile phase consisting of methanol-acetonitrile-trifluoroacetic acid-triethylamine at a ratio of 80/20/0.1/0.5 (v/v/v/v) was used. The comparison of the chromatographic behaviors for the resolution of fendiline and its analogues indicated that the 3,3-diphenylpropyl group bonded to the secondary amino group of fendiline is important in the chiral recognition and the difference in the steric bulkiness between the phenyl group and the methyl group at the chiral center of fendiline is also important in the chiral recognition.
- Lee, Ga Ram,Hyun, Myung Ho
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p. 21386 - 21397
(2015/02/19)
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- PROCESS FOR THE RACEMIZATION OF OPTICALLY ACTIVE ARYLALKYLAMINES
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Many optically active amines are valuable pharmaceuticals and intermediates for the preparation of active compounds. It is frequently the case that only one of the two enantiomers is active or not harmful, so that isolation of this enantiomer from the racemic mixture is necessary. Processes for racemate resolution make it possible to separate racemic mixtures into their enantiomers. Here, it is useful to once again racemize the enantiomer which is not required and recirculate it to racemate resolution and thus improve the yield of the desired enantiomer. The present invention relates to processes for the racemization of optically active amines, in particular arylalkylamines, in the presence of hydrogen and a hydrogenation/dehydrogenation catalyst comprising nickel, cobalt and copper as active components at elevated temperature.
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Paragraph 0117
(2014/02/15)
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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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- Efficient synthesis and practical resolution of 1-(naphthalen-1-yl) ethanamine, a key intermediate for cinacalcet
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An efficient synthesis of 1-(naphthalen-1-yl)ethanamine (RS-2) and its practical resolution to optically pure (1R)-(naphthalen-1-yl)ethanamine (R-(+)-2), a key intermediate in the synthesis of cinacalcet hydrochloride (1), is described. The resolution of RS-2 using R-(-)-mandelic acid as a resolving agent in ethanol was established on an industrial scale to give pure R-(+)-2 with >99.8% ee after liberation of the amine from its mandelate salt. An efficient process for the racemization of undesired isomer S-(-)-2 is also provided to maximize the yield of desired enantiomer.
- Mathad, Vijayavitthal T.,Shinde, Gorakshanath B.,Ippar, Sharad S.,Niphade, Navnath C.,Panchangam, Raghavendra K.,Vankawala, Pravinchandra J.
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p. 341 - 346
(2011/04/15)
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- Heterogeneous raney nickel and cobalt catalysts for racemization and dynamic kinetic resolution of amines
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Raney metals were studied as heterogeneous catalysts for racemization and dynamic kinetic resolution (DKR) of chiral amines, as an alternative to metals like palladium or ruthenium. Both Raney nickel and cobalt were able to selectively racemize various chiral amines with high selectivity. In the racemization of benzylic primary amines, the minor formation of side products, e.g., secondary amines, can be suppressed by varying the hydrogen pressure. In the racemization of aliphatic amines over Raney catalysts, the selectivity is very high, with the enantiomeric amine as the sole product. DKR of racemic aliphatic amines can be performed with immobilized Candida antarctica lipase B and Raney nickel in one pot; for 2-hexylamine, a yield of 95% of the acetylated amide was achieved, with 97% ee. Attention is devoted to the compatibility of the enzyme and the metal catalyst during the DKR. For benzylic primary amines, a two-pot process is proposed in which the liquid is alternatingly shuttled between two vessels containing the solid racemization catalyst and the biocatalyst. After 4 such cycles, the amide of (R)-1-phenylethylamine was obtained with 94% yield and more than 90% ee.
- Parvulescu, Andrei N.,Jacobs, Pierre A.,De Vos, Dirk E.
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scheme or table
p. 113 - 121
(2009/04/16)
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- PROCESSES FOR THE PREPARATION OF CINACALCET
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There are described several processes for making a free base of cinacalcet. One of the described processes goes through an intermediate of the formula (II) where R1 and R2 are both hydrogen, or R1 and R2, together, form a double bond.
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Page/Page column 23-24
(2008/12/05)
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- Arylalkylamine vanadium (V) salts for the treatment and/or prevention of Diabetes mellitus
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This invention provides compounds of formula (IIA) and pharmaceutical compositions thereof, where M, a, b, and R1-R5 are as defined herein, for treating human type 1 and type 2 diabetes, particularly insulin-resistant diabetes. Pharmaceutical compositions comprising the compounds of formula (IIA) are also disclosed.
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Page/Page column 19; 20
(2010/11/26)
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- New efficient substrates for semicarbazide-sensitive amine oxidase/VAP-1 enzyme: Analysis by SARs and computational docking
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Structure activity relationships for semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1) were studied using a library of arylalkylamine substrates, with the aim of contributing to the discovery of more efficient SSAO substrates. Experimental data were contrasted with computational docking studies, thereby allowing us to examine the mechanism and substrate-binding affinity of SSAO and thus contribute to the discovery of more efficient SSAO substrates and provide a structural basis for their interactions. We also built a model of the mouse SSAO structure, which provides several structural rationales for interspecies differences in SSAO substrate selectivity and reveals new trends in SSAO substrate recognition. In this context, we identified novel efficient substrates for human SSAO that can be used as a lead for the discovery of antidiabetic agents.
- Yraola, Francesc,García-Vicente, Silvia,Fernández-Recio, Juan,Albericio, Fernando,Zorzano, Antonio,Marti, Luc,Royo, Miriam
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p. 6197 - 6208
(2007/10/03)
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- Transfer hydrogenation process
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A catalytic transfer hydrogenation process is provided. The process can be employed to transfer hydrogenate N-substituted imines and iminium salts, which are preferably prochiral. The catalyst employed in the process is preferably a metal complex with one hydrocarbyl or cyclopentadienyl ligand and which is also coordinated to defined bidentate ligands. Preferred metals include rhodium, ruthenium and iridium. Preferred bidentate ligands are diamines and aminoalcohols, particularly those comprising chiral centres. The hydrogen donor is advantageously a mixture of triethylamine and formic acid. A process for the production of primary and secondary amines using the catalytic transfer hydrogenation of the N-substituted imines and iminium salts is also provided.
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Page column 29
(2008/06/13)
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- Method for producing optically active chrysanthemic acid
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Disclosed is a method for producing an optically active chrysanthemic acid, which method is characterized by optical resolution of a chrysanthemic acid having a trans isomer ratio of not less than 70% and an optical purity of 2% e.e. to less than 10% e.e. with an optically active organic.
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- 2-aminobenzoxazole derivatives and combinatorial libraries thereof
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The present invention relates to novel 2-aminobenzoxazole derivative compounds of the following formula: wherein R1 to R4 and Z have the meanings provided herein. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing 2-aminobenzoxazole derivative compounds.
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- Process for producing L-ambrox
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(-)-2,5,5,8a-Tetramethyl-1-(carboxymethyl)-2-hydroxydecalin is subjected to lactonization by dehydration to form decahydro-3a,6,6,9a-tetramethyl(3aα,5aβ,9aα,9bβ)-(+)-naphtho[2,1-b]furan-2(1H)-one, which is then reduced with a metal hydride to convert it into (-)-2,5,5,8a-tetramethyl-1-(carboxymethyl)-2-hydroxydecalin, followed by dehydrative cyclization to give L-ambrox. The (-)-2,5,5,8a-tetramethyl-1-(carboxymethyl)-2-hydroxydecalin is produced from its racemic mixture. The resolution is performed using a 1-(aryl)ethylamine. The starting material for the synthesis is beta-ionone.
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- Saponification agents. 2. Synthesis of arylisocyanates with ethyl lactate and their use in racemic bases saponification
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Reaction of the arylisocyanates 2a-c with ethyl (S)-(-)-lactate, followed by careful saponification, afforded the corresponding chiral acids (S)-(-)- 4a-c. The latter were successfully used for the resolution of various racemic bases belonging to both the ephedrine and α-aryl ethylamine series.
- Brown,Moudachirou
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p. 10309 - 10320
(2007/10/02)
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- OPTICALLY ACTIVE F-2-ISOPROPOXYPROPIONIC ACID: A NOVEL DERIVATIZING AGENT FOR GAS CHROMATOGRAPHIC ANALYSIS
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F-2-Isopropoxypropionic acid (PIPA) was resolved into enantiomers via its diastereomeric (+)-1-phenylethylamide. (+)-F-2-Isopropoxypropionyl derivatives of several chiral 1-arylalkylamines and α-amino acids were effectively resolved by gas chromatography at low temperature.
- Kawa, Hajimu,Yamaguchi, Fumihiko,Ishikawa, Nobuo
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p. 745 - 748
(2007/10/02)
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- Preparation of esters of phosphorus acids
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Esters of phosphorus acids are prepared by an improved process whereby aromatic alcohols and phosphorus halides are reacted at specified temperatures in the presence of amine catalysts thereby providing high yields of substantially pure esters and allowing preparation of selected halogen-containing mono- and di-esters of phosphorus acids wherein halogen is directly bonded to phosphorus having substantially no side reactant contamination. The phosphorus esters are useful as intermediates in the preparation of plasticizers, oil additives and functional fluids.
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