- Hybrid catalysis of 8-quinolinecarboxaldehyde and br?nsted acid for efficient racemization of α-amino amides and its application in chemoenzymatic dynamic kinetic resolution
-
The combination of 8-quinolinecarboxaldehyde and benzoic acid proved to be an effective catalyst system for the racemization of N-unprotected α-aryl- or α-alkyl-substituted α-amino amides. Application of this system to chemoenzymatic dynamic kinetic resolution provided an efficient access to enantiomerically pure N-acetyl-α-amino amides in good to high yields.
- Kiyokawa, Mari,Nagato, Yuya,Ohmatsu, Kohsuke,Ooi, Takashi,Shirai, Yuto
-
-
- COMPLEMENT MODULATORS AND RELATED METHODS
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The present disclosure presents compounds and compositions that interact with complement components. Some compounds inhibit complement activity. Included are small molecule compounds and compositions that function as C5 inhibitor compounds. Methods for inhibiting complement activity and methods of treating complement-related indications with the C5 inhibitor compounds and compositions are provided.
- -
-
Paragraph 0422
(2020/10/20)
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- Highly Active Chiral Dilithium(I) Binaphthyldisulfonate Catalysts for Enantio- And Chemoselective Strecker-Type Reactions
-
An enantioselective Strecker-type reaction of aldimines and ketimines was developed by using a chiral dilithium(I) binaphthyldisulfonate as a chiral acid-base cooperative catalyst. The present catalytic system features an extremely short reaction time (10 min to 4 h), unlike conventional catalytic systems. Along with the design of stronger chiral Li(I) Lewis acid catalysts, a highly reactive pentacoordinate silicate generated in situ could promote the reactions. In particular, instead of unstable N-Bn Strecker products, more stable N-CH2(9-anthryl) and N-CH2(1-naphthyl) Strecker products could be obtained in high yields with high enantioselectivities. By a switch of the present and previous catalyst systems, chemoselective cyanation to a ketoaldimine could be performed, respectively. Moreover, mechanistic investigations provided useful information regarding the active catalysts, catalytic cycles, and possible transition states.
- Hatano, Manabu,Nishio, Kosuke,Mochizuki, Takuya,Nishikawa, Keisuke,Ishihara, Kazuaki
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p. 8178 - 8186
(2019/08/22)
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- RETRACTED ARTICLE: Chemoenzymatic Method for Enantioselective Synthesis of (R)-2-Phenylglycine and (R)-2-Phenylglycine Amide from Benzaldehyde and KCN Using Difference of Enzyme Affinity to the Enantiomers
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In general, enzymatic and chemoenzymatic methods for asymmetric synthesis of α-amino acids are performed using highly enantioselective enzymes. The enzymatic reactions using α-aminonitrile as a starting material have been performed using reaction conditions apart from the chemical Strecker synthesis. We developed a new chemoenzymatic method for the asymmetric synthesis of α-amino acids from aldehydes and KCN by performing Strecker synthesis and nitrilase reaction in the same reaction mixture. Nitrilase AY487533 that showed rather low enantioselectivity in hydrolysis of 2-phenylglycinonitrile (2PGN) to 2-phenylglycine (2PG) was utilized in the hydrolysis of aminonitrile formed from benzaldehyde and KCN via 2PGN by Strecker synthesis, preferentially synthesizing (R)-2PG with more than 95 % yield and enantiomeric excess (ee). The method was also utilized for the synthesis of (R)-2-phenylglycine amide ((R)-2PGNH2) from benzaldehyde and KCN by the chemoenzymatic reaction in the presence of a mutated nitrilase AY487533W186A, which catalyzes the conversion of 2PGN to 2PGNH2.
- Kawahara, Nobuhiro,Asano, Yasuhisa
-
p. 5014 - 5020
(2018/10/20)
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- Synthetic method for chiral alpha-aminoamide compounds
-
The invention provides a synthetic method for chiral alpha-aminoamide compounds, belongs to the technical field of organic synthetic methodology, and concretely relates to a synthetic method for chiral alpha-aminoamide compounds, wherein the method has a simple process, low costs and good economy. The method comprises the following steps: 1, performing ammonolysis: adding substituted chiral alpha-aminocarboxylate hydrochloride into concentrated ammonia water, performing stirring for 4-12h under a room temperature, wherein each 1mmol substituted chiral alpha-aminocarboxylate hydrochloride is corresponding to 2-8mL the concentrated ammonia water; 2, after a reaction is finished, performing distillation for removing ammonia water after the reaction to obtain crude products chiral alpha-aminoamide compounds; and 3, performing filtration on the obtained crude products chiral alpha-aminoamide compounds by adopting a manner of adding a solvent or performing purification on the obtained crude products chiral alpha-aminoamide compounds through a manner of column chromatography which uses ammonia water as a mobile phase to obtain the products chiral alpha-aminoamide compounds. Compared with the prior art, a large number of an ammonia gas for ammonolysis is not needed in the method, the process and post-treatment are simple, costs are low and reaction time is short.
- -
-
Paragraph 0039; 0040; 0041
(2018/01/11)
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- Enantioselective ammonolysis of phenylglycine methyl ester with lipase-pluronic nanoconjugate in tertiary butanol
-
Asymmetrical ammonolysis of (R)- and (S)-phenylglycine methyl ester was carried out by using a lipase (CALB)-polymer (Pluronic) nanoconjugate as the catalyst, displaying a 11-fold increased catalytic rate compared to the free CALB in tertiary butanol. Graphical Abstract: The asymmetrical ammonolysis of (R)- and (S)-phenylglycine methyl ester was accomplished using a lipase-Pluronic nanoconjugate, displaying a 11-fold higher catalytic rate compared to the free lipase.[Figure not available: see fulltext.]
- Wu, Xiaoling,Wang, Rui,Zhang, Yifei,Ge, Jun,Liu, Zheng
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p. 1407 - 1410
(2014/08/18)
-
- CHIRAL FLUORINATING REAGENTS
-
This invention relates to fluorinating agents and, more particularly, to chiral non-racemic fluorinating agents useful for enantioselective fluorination, as well as to their synthesis and use and other subject matter. The fluorinating agents are based on a substituted 1,4-diazabicyclo[2.2.2]octane (DABCO) skeleton and provide electrophillic fluorine enantioselectively.
- -
-
Page/Page column 44
(2014/05/24)
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- BENZAMIDES AND NICOTINAMIDES AS SYK MODULATORS
-
The present invention is directed to compounds of formula I and pharmaceutically acceptable salts, esters, and prodrugs thereof which are inhibitors of Syk kinase. The present invention is also directed to intermediates used in making such compounds, the preparation of such a compound, pharmaceutical compositions containing such a compound, methods of inhibition Syk kinase activity, methods of inhibition the platelet aggregation, and methods to prevent or treat a number of conditions mediated at least in part by Syk kinase activity, such as Non Hodgkin's Lymphoma.
- -
-
Page/Page column 89-90
(2012/05/20)
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- Preparation of cross-linked enzyme aggregates of l-aminoacylase via co-aggregation with polyethyleneimine
-
l-Aminoacylase from Aspergillus melleus was co-aggregated with polyethyleneimine and subsequently cross-linked with glutaraldehyde to obtain aminoacylase-polyethyleneimine cross-linked enzyme aggregates (termed as AP-CLEA). Under the optimum conditions, AP-CLEA expressed 74.9% activity recovery and 81.2% aggregation yield. The said method of co-aggregation and cross-linking significantly improved the catalytic stability of l-aminoacylase with respect to temperature and storage. AP-CLEA were employed for enantioselective synthesis of three unnatural amino acids (namely: phenylglycine, homophenylalanine and 2-naphthylalanine) via chiral resolution of their ester-, amide- and N-acetyl derivatives. The enantioselectivity of AP-CLEA was the highest for hydrolysis of amino acid amides; was moderate for hydrolysis of N-acetyl amino acids and was the least for hydrolysis of amino acid esters. Furthermore, AP-CLEA were found to retain more than 92% of the initial activity after five consecutive batches of (RS)-homophenylalanine hydrolysis suggesting an adequate operational stability of the biocatalyst.
- Vaidya, Bhalchandra K.,Kuwar, Suyog S.,Golegaonkar, Sandeep B.,Nene, Sanjay N.
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experimental part
p. 184 - 191
(2012/03/22)
-
- Catalyst development for organocatalytic hydrosilylation of aromatic ketones and ketimines
-
A new family of Lewis basic 2-pyridyl oxazolines have been developed, which can act as efficient organocatalysts for the enantioselective reduction of prochiral aromatic ketones and ketimines with trichlorosilane, a readily available and inexpensive reagent. 1-Isoquinolyl oxazoline, derived from mandelic acid, was identified as the most efficient catalyst of the series, capable of delivering high enantioselectivities in the reduction of both ketones (up to 94% ee) and ketimines (up to 89% ee).
- Malkov, Andrei V.,Stewart-Liddon, Angus J. P.,McGeoch, Grant D.,Ramirez-Lopez, Pedro,Kocovsky, Pavel
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scheme or table
p. 4864 - 4877
(2012/07/28)
-
- Probing the enantioselectivity of a diverse group of purified cobalt-centred nitrile hydratases
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In this study a diverse range of purified cobalt containing nitrile hydratases (NHases, EC 4.2.1.84) from Rhodopseudomonas palustris HaA2 (HaA2), Rhodopseudomonas palustris CGA009 (009), Sinorhizobium meliloti 1021 (1021), and Nitriliruptor alkaliphilus (iso2), were screened for the first time for their enantioselectivity towards a broad range of chiral nitriles. Enantiomeric ratios of >100 were found for the NHases from HaA2 and CGA009 on 2-phenylpropionitrile. In contrast, the Fe-containing NHase from the well-characterized Rhodococcus erythropolis AJ270 (AJ270) was practically aselective with a range of different α-phenylacetonitriles. In general, at least one bulky group in close proximity to the α-position of the chiral nitriles seemed to be necessary for enantioselectivity with all NHases tested. Nitrile groups attached to a quaternary carbon atom were only reluctantly accepted and showed no selectivity. Enantiomeric ratios of 80 and >100 for AJ270 and iso2, respectively, were found for the pharmaceutical intermediate naproxennitrile, and 3-(1-cyanoethyl)benzoic acid was hydrated to the corresponding amide by iso2 with an enantiomeric ratio of >100.
- Van Pelt,Zhang,Otten,Holt,Sorokin,Van Rantwijk,Black,Perry,Sheldon
-
experimental part
p. 3011 - 3019
(2011/06/17)
-
- Towards racemizable chiral organogelators
-
A chiral organogelator has been synthesized that can be racemized and self-assembled in apolar solvents whilst at higher concentrations organogels are formed. Field emission scanning and transmission electron microscopy revealed the formation of bundle fibrils that are able to gelate the solvent. 1H NMR studies showed hydrogen-bond interactions between the peptide head groups of neighbouring organogelator molecules. The enantiomerically pure organogelator can be racemized by the base DBU (1,8-diazabicyclo[5.4.0]undec-7- ene) as was evident from chiral high-performance liquid chromatography analysis.
- Lin, Jian Bin,Dasgupta, Debarshi,Cantekin, Seda,Schenning, Albertus P. H. J.
-
experimental part
p. 960 - 965
(2011/03/20)
-
- Enantioselective conversion of α-arylnitriles by Klebsiella oxytoca
-
A new bacterial isolate Klebsiella oxytoca 38.1.2 with stereoselective nitrile hydratase activity against rac-2-phenylglycine nitrile, rac-2-phenylpropionitrile and rac-mandelonitrile was investigated. The cultivation conditions for growth and nitrile hydratase formation were studied. An intracellular (S)-enantioselective nitrile hydratase and a putative (S)-selective amidase were found to be induced in the presence of rac-2-phenylpropionitrile. The temperature dependence on the enantioselectivity of the nitrile hydratase active cells was studied in more detail for the biotransformation of rac-2-phenylpropionitrile and rac-mandelonitrile. By increasing the temperature from 15 °C to 37 °C, the apparent enantiomeric ratio of the conversion of rac-2-phenylpropionitrile to (S)-2-phenylpropionamide increased from 16 to 35 at nearly 50% conversion rate. rac-Mandelonitrile was converted to (S)-mandelamide with an enantiomeric excess of up to 95% in a 80% yield without further conversion to mandelic acid.
- Ewert, Christian,Lutz-Wahl, Sabine,Fischer, Lutz
-
body text
p. 2573 - 2578
(2009/04/06)
-
- Emergence of a single solid chiral state from a nearly racemic amino acid derivative
-
The evolution of a single chiral solid state is reported for an amino acid derivative starting from a nearly racemic mixture of solid left- and right-handed crystals. Attrition-enhanced dissolution and recrystallization processes based on solubility considerations of the Gibbs-Thomson rule, coupled with solution-phase racemization, drive this near-equilibrium system inexorably to single chirality in the solid phase. Copyright
- Noorduin, Wim L.,Izumi, Toshiko,Millemaggi, Alessia,Leeman, Michel,Meekes, Hugo,Van Enckevort, Willem J. P.,Kellogg, Richard M.,Kaptein, Bernard,Vlieg, Elias,Blackmond, Donna G.
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p. 1158 - 1159
(2008/09/20)
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- Asymmetric catalysis of carbon-carbon bond forming reactions using amino acid-derived C1-symmetrical salen ligands
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Four amino acids (alanine, valine, phenylalanine and phenylglycine) have been converted into C1-symmetrical salen ligands and complexed to titanium, vanadium, copper and cobalt. The resulting complexes have been used as asymmetric catalysts for asymmetric cyanohydrin synthesis, asymmetric Strecker reactions, asymmetric synthesis of α-methyl amino acids and asymmetric Darzens condensations. Satisfactory levels of asymmetric induction were obtained from reactions in which the (salen)metal complex acts as a chiral Lewis acid, but low levels of asymmetric induction were obtained from reactions carried out under solid-liquid phase-transfer conditions.
- Belokon, Yuri N.,Hunt, Jamie,North, Michael
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experimental part
p. 2804 - 2815
(2009/06/28)
-
- Methods and compositions for treating amyloid-related diseases
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Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-related disease.
- -
-
Page/Page column 137
(2010/11/24)
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- Asymmetric allylic substitution catalyzed by C1-symmetrical complexes of molybdenum: Structural requirements of the ligand and the stereochemical course of the reaction
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Application of new chiral ligands (R)-(-)-12a and (S)-(+)-12c (VALDY), derived from amino acids, to the title reaction, involving cinnamyl (linear) and isocinnamyl (branched) type substrates (4 and 5 → 6), led to excellent regio- and enantioselectivities (>30:1, ≤98% ee), showing that ligands with a single chiral center are capable of high asymmetric induction. The structural requirements of the ligand and the mechanism are discussed. The application of single enantiomers of deuterium-labeled substrates (both linear 38c and branched 37c) and analysis of the products (41-43) by 2{ 1H) NMR spectroscopy in a chiral liquid crystal matrix allowed the stereochemical pathways of the reaction to be distinguished. With ligand (S)-(+)-12c, the matched enantiomer of branched substrate was found to be (S)-5, which was converted into (R)-6 with very high regio- and stereoselectivity via a process that involves net retention of stereochemistry. The mismatched enantiomer of the branched substrate was found to be (R)-5, which was also converted into (R)-6, that is, with apparent net inversion, but at a lower rate and with lower overall enantioselectivity. This latter feature, which may be termed a "memory effect", reduced the global enantioselectivity in the reaction of the racemic substrate (±)-5. The stereochemical pathway of the mismatched manifold has been shown also to be one of net retention, the apparent inversion occurring through equilibration via an Mo-allyl intermediate prior to nucleophilic attack. Incomplete equilibration leads to the memory effect and thus to lower enantioselectivity. Analysis of the mismatched manifold over the course of the reaction revealed that the memory effect is progressively attenuated with the nascent global selectivity increasing substantially as the reaction proceeds. The origin of this effect is suggested to be the depletion of CO sources in the reaction mixture, which attenuates turnover rate and thus facilitates greater equilibrium. The linear substrate was also converted into the branched product with net syn stereochemistry, as shown by isotopic labeling. An analogous process operates in the generation of small quantities of linear product from branched substrate.
- Malkov, Andrei V.,Gouriou, Laure,Lloyd-Jones, Guy C.,Stary, Ivo,Langer, Vratislav,Spoor, Paul,Vinader, Victoria,Kocovsky, Pavel
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p. 6910 - 6929
(2007/10/03)
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- Synthesis of optically active α-methylamino acids and amides through biocatalytic kinetic resolution of amides
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Catalyzed by Rhodococcus sp. AJ270, a nitrile hydratase and amidase containing microbial whole-cell catalyst, under very mild conditions, a number of racemic α-methylamino amides were resolved into the corresponding optically active (S)-(+)-α-methylamino acids and (R)-(-)-α- methylamino amides. The steric requirement of the amidase against α-amino phenylacetamides bearing methyl group(s) at α-amino nitrogen and/or α-carbon was also studied. Coupled with the chemical hydrolysis of amide, the biotransformation process provided a direct synthesis of α-methylamino acids in both enantiomeric forms from readily available racemic amides.
- Wang, Mei-Xiang,Liu, Jun,Wang, De-Xian,Zheng, Qi-Yu
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p. 2409 - 2416
(2007/10/03)
-
- Stereoselective hydration of (RS)-phenylglycine nitrile by new whole cell biocatalysts
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Five new bacterial isolates with stereoselective nitrile hydratase activity against (RS)-2-phenylpropionitrile and (RS)-phenylglycine nitrile were investigated. The permeabilized whole cell isolates selectively hydrate the (S)-enantiomer of phenylglycine nitrile with E values of 1.2-5.4. One isolate, which was identified as Pantoea endophytica, produced pure (S)-phenylglycine (>99% ee) as a result of hydrolysis of (S)-phenylglycine amide by an (S)-specific amidase. Surprisingly, in the hydrolysis of (RS)-phenylglycine nitrile, it was found that the (R)-amide was accumulated in excess (21% ee) despite the nitrile hydratase produced by Pantoea endophytica was (S)-selective. The synthesis of pure (R)-phenylglycine (>99% ee) was achieved in time course studies using another Pantoea sp. with (R)-selective amidase. In the case of Nocardioides sp. the intermediate product, (S)-phenylglycine amide, could be produced (52% ee) without its subsequent hydrolysis into the acid due to the apparent absence of any amidase activity.
- Hensel, Martina,Lutz-Wahl, Sabine,Fischer, Lutz
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p. 2629 - 2633
(2007/10/03)
-
- Practical and convenient enzymatic synthesis of enantiopure α-amino acids and amides
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Catalyzed by the nitrile hydratase and the amidease in Rhodococcus sp. AJ270 cells under very mild conditions, a number of α-aryl- and α-alkyl-substituted DL-glycine nitriles 1 rapidly underwent a highly enantioselective hydrolysis to afford D-(-)-α-amino acid amides 2 and L-(+)-α-amino acids 3 in high yields with excellent enantiomeric excesses in most cases. The overall enantioselectivity of the biotransformations of nitriles originated from the combined effects of a high L-enantioselective amidase and a low enantioselective nitrile hydratase. The influence of the substrates on both reaction efficiency and enantioselectivity was also discussed in terms of steric and electronic effects. Coupled with chemical hydrolysis of D-(-)-α-phenylglycine amide, biotransformation of DL-phenylglycine nitrile was applied in practical scale to produce both D- and L-phenylglycines in high optical purity.
- Wang, Mei-Xiang,Lin, Shuang-Jun
-
p. 6542 - 6545
(2007/10/03)
-
- Highly efficient and enantioselective synthesis of L-arylglycines and D-arylglycine amides from biotransformations of nitriles
-
Under very mild conditions, the Rhodococcus sp. AJ270-catalysed biotransformation of arylglycine nitriles 1, prepared easily from the reaction of substituted benzaldehydes, ammonium chloride and potassium cyanide, proceeded efficiently to produce optically active D-arylglycine amides 2 and L-arylglycines 3 in excellent yields with enantiomeric excesses higher than 99%.
- Wang, Mei-Xiang,Lin, Shuang-Jun
-
p. 6925 - 6927
(2007/10/03)
-
- Asymmetric molybdenum(0)-catalyzed allylic substitution
-
Application of new ligands (R)-(-)-8,(S)-(+)-16, and (S)-(+)-17 to the title reaction (1 or 2 → 3) led to excellent regio- and enantioselectivities (> 30:1; ≤ 98% ee); although lacking the C2-symmetry, the catalysts can be viewed as quasi-C2-symmetrical since the single chiral center is sufficient to determine the sense of wrapping of the metal by the ligand.
- Malkov, Andrei V.,Spoor, Paul,Vinader, Victoria,Ko?ovsky, Pavel
-
p. 509 - 512
(2007/10/03)
-
- Stereoretentive nitrile hydratase-catalysed hydration of d-phenylglycine nitrile
-
The hydration of D-phenylglycine nitrile to the corresponding amide, mediated by nitrile hydratase-containing microorganisms, was studied. Batch and fed-batch reactions were compared with regard to degradation and racemisation of the chemically labile substrate. A batch process gave satisfactory results and at up to 25 mM D-phenylglycine nitrile (D-1), D-phenylglycine amide was obtained in 94% yield with 92% ee using an immobilised Rhodococcus sp. (NOVO SP 361). The enzyme could be reused, although it slowly lost its activity. When the concentration of D-phenylglycine nitrile was increased to 100 mM in a batch reaction rapid decomposition of the substrate was observed and D-phenylglycine amide was obtained in only 37% yield. A fed-batch reaction afforded an improved yield, although the decomposition of the substrate could not be avoided completely. Lowering the temperature stabilised the substrate, and a fed-batch reaction at 5 °C resulted in a 96% yield of D-phenylglycine amide with 95% ee. A number of other whole-cell hydratase/amidase systems also hydrated D-1 in nearly quantitative yield and >94% ee. Moreover, the ee was further increased to >99% upon prolonged reaction times with minimal loss in yield due to the action of the L-specific amidase that is present in these biocatalysts.
- Wegman,Heinemann,Stolz,Van Rantwijk,Sheldon
-
p. 318 - 322
(2013/08/07)
-
- A catalytic asymmetric Strecker-type reaction promoted by Lewis acid-Lewis base bifunctional catalyst
-
A general asymmetric Strecker-type reaction is reported, catalyzed by the Lewis acid-Lewis base bifunctional catalyst 1. The reaction of trimethylsilyl cyanide (TMSCN) with various fluorenyl imines, including n-aldimines and α,β-unsaturated imines, proceeds with good to excellent enantioselectivities in the presence of a catalytic amount of phenol as additive (20 mol%) (catalytic system 1). The products were successfully converted to the corresponding amino acid derivatives in high yields without loss of enantiomeric purity. Furthermore, hydrogenation or dihydroxylation of the products from α,β-unsaturated imines afforded saturated or functionalized aminonitriles also without loss of enantiomeric purity. The absolute configuration of the products and a control experiment using catalyst 2 supported the proposed dual activation of the imine and TMSCN by the Lewis acid (Al) and the Lewis base moiety (phosphine oxide) of 1. From the mechanistic studies including kinetic and NMR experiments of the catalytic species, the role of PhOH seems to be a proton source to protonate the anionic nitrogen of the intermediate. Specifically, we have found that TMSCN is more reactive than HCN in this catalytic system, probably due to the activation ability of the phosphine oxide moiety of 1 toward TMSCN. This fact prompted us to develop the novel catalytic system 2, consisting of 1 (9 mol%), TMSCN (20 mol%) and HCN (1.2 mol eq). This new system afforded comparable results with obtained by system 1 (1 (9 mol%)-TMSCN (2 mol eq)-PhOH (20 mol%)).
- Takamura,Hamashima,Usuda,Kanai,Shibasaki
-
p. 1586 - 1592
(2007/10/03)
-
- Dynamic kinetic resolution of phenylglycine esters via lipase-catalysed ammonolysis
-
Ammonolysis of D,L-phenylglycine methyl ester catalysed by Novozym 435 at 40°C in tert-butyl alcohol gave D-phenylglycine amide in 78% ee at 46% conversion, corresponding to an enantiomeric ratio (E) of 16. Lowering the temperature improved the enantioselectivity (E = 52 at -20°C). Combination of ammonolysis with pyridoxal-catalysed in situ racemisation of the unconverted ester (dynamic kinetic resolution), at -20°C, gave D- phenylglycine amide with 88% ee at 85% conversion. The amide racemised much slower than the ester at this low temperature.
- Wegman,Hacking,Rops,Pereira,Van Rantwijk,Sheldon
-
p. 1739 - 1750
(2007/10/03)
-
- Enantioselective synthesis of α-amino nitriles from N-benzhydryl imines and HCN with a chiral bicyclic guanidine as catalyst
-
(Equation Presented) A novel catalytic enantioselective Strecker synthesis of chiral α-amino nitriles and α-amino acids is described and analyzed with regard to the possible mechanistic basis for stereoselectivity. Key features of the enantioselective process include (1) the use of the chiral bicyclic guanidine 1 as catalyst and (2) the use of the N-benzhydryl substituent on the imine substrate.
- Corey,Grogan, Michael J.
-
p. 157 - 160
(2008/03/11)
-
- Auxiliary chiral ketones in the asymmetric synthesis of α-amino acids by Strecker reaction
-
The asymmetric synthesis of α-aminoamides 1 R1CH(CONH2)NH2 1 = Ph-CH2, 1b: R1 = Pri, 1c: R1 = Ph> that leads to the corresponding α-amino acids is achieved by a classical Strecker reaction 1CHO, HCN, NH3> using an auxiliary chiral ketone (R2R'2CO) as a catalyst.In the presence of an aqueous solution of HCN and NH3, the (-)-5R-(methylethenyl)-3R-cyano-2R-methylcyclohexanone 2(-) leads to the 5R-(methylethenyl)-3R-cyano-2R-methyl-1R-cyano-cyclohexylamine 3 with 80percent stereoselectivity.Following condensation with R1CHO, this α-aminonitrile R2R'2C(CN)NH2 3 yields the corresponding iminonitrile which undergoes a second asymmetric addition of HCN yielding an asymmetric α-aminodinitrile 4 R2R'2C(CN)-NH-CHR1(CN) with stereoselectivity that varies betweeen 62percent (R1 = Ph) and 79percent (R1 = Ph-CH2).The α-aminodinitrile obtained as the major product undergoes regioselective hydration of the secondary aminonitrile moiety followed by the decomposition ("retro-Strecker") of the tertiary aminonitrile moiety yielding an optically active α-aminoamide (eg 78percent optical purity for 1a) and the auxiliary chiral ketone 2 and ketonic derivatives.Keywords - α-aminonitrile / α-amino acid / asymmetric synthesis
- Bousquet, C.,Tadros, Z.,Tonnel, J.,Mion, J.,Taillades, J.
-
p. 513 - 520
(2007/10/02)
-
- Influence of a Hydroalcoholic Solvent on the Enantioselectivity of α-Amino nitrile Hydration Catalysed by Chiral Ketones
-
The enantioselective hydration of α-aminonitriles 1, RCH(CN)NH2 i; 1c: R = Ph> has been achieved in an alkaline hydroalcoholic medium in the presence of chiral ketonic catalysts.Of the different ketones used, (-)-(5R,3R,2R)-5-(methylethenyl)-3-cyano-2-methylcyclohexanone (8) gives rise to significant enantioselectivity D/kL = 2.1; T = 10 deg C; solvent, water-propan-2-ol (45:55,v/v)>.Although the structure of the catalyst could probably be improved, we show in this paper that the efficiency and especiallythe enantioselectivity of the catalyst are not only under steric control but also depend on the nature and composition of the hydroalcoholic solvent.Thus, for the three aminonitriles studied in the presence of the catalyst 8, the increase in percentage of propan-2-ol favours the hydration of the D α-aminonitrile as shown for the hydration of 1c for which the ratio kD/kL increases threefold when the percentage of propan-2-ol increases from 10 to 95percent.
- Lagriffoul, Pierre-Henri,Tadros, Ziad,Taillades, Jacques,Commeyras, Auguste
-
p. 1279 - 1285
(2007/10/02)
-
- Synthesis of Chiral Atropoisomeric Square-planar Nickel(II) and Copper(II) Complexes formed by Macrocyclic Ligands containing Pendant Polyether Groups and a Quaternary Ammonium Group
-
Novel copper(II) and nickel(II) complexes of macrocyclic Schiff bases formed from derivatives of N,N'-bis(2-benzoylphenyl)oxamide and 1,2-diaminoethane have been prepared.In one case, separation of atropoisomeric chiral complexes has been achieved by preparative chromatography on SiO2.Quaternization of some of the complexes with an excess of MeI affords chiral complexes possessing a positively charged quaternary ammonium group and polyether podands in addition to a weakly electrophilic metal site.
- Belokon, Yuri N.,Pritula, Ludmila K.,Tararov, Vitali I.,Bakhmutov, Vladimir I.,Struchkov, Yuri T.,et al.
-
p. 1867 - 1872
(2007/10/02)
-
- ENANTIOSPECIFIC SYNTHESIS OF A RIGID, C2 SYMMETRIC, CHIRAL GUANIDINE BY A NEW AND DIRECT METHOD
-
A broadly applicable method has been demonstrated for the efficient synthesis of chiral bicyclic guanidines such as 1 from chiral α-amino acids.
- Corey, E. J.,Ohtani, Mitsuaki
-
p. 5227 - 5230
(2007/10/02)
-
- Quantitative Approaches to Optical Resolution. Part 1. Resolution of DL-Phenylglycine Derivatives with (+)-Tartaric Acid
-
The results of 23 cases of resolution of DL-phenyldlycine derivatives (I) with (+)-tartaric acid in various solvents are investigated, using correlation analysis, as a function of the introduced racemic compounds and the solvent used.A procedure, combining three quantitative structure-activity relationship methods, i.e.Golender and Rozenblit's logico-structural approach with the Free-Wilson and Hansch analyses, resulted in statistically significant relationships.It is suggested that the solvent may exert two kinds of influence: (1) the higher the solvent polarity, the more likely the L-(I) salt to crystallise; (2) alcoholic mixtures, although being highly polar, favour the precipitation of the D-(I) salt rather than that of the L-(I) salt, probably due to a selective interaction with the diastereomers.As to the racemic compound, the relationships obtained are in accord with literature statements that resolution proceeds by a multiple interaction mechanism.
- Lopata, Antal,Faigl, Ferenc,Fogassy, Elemer,Darvas, Ferenc
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p. 2930 - 2952
(2007/10/02)
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- Ueber die Enantiomerentrennung durch Verteilung zwischen fluessigen Phasen 3. Mitteilung. Selektivitaet der lipophilen Weinsaeureester fuer chirale Ammonium-Salze verschiedener Konstitution und Konfiguration
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Several methods are described which allow determination on a small scale of the enantiomer distribution constant Q, and the affinity coefficient P, which characterize the enantioselectivity and the affinity of a lipophilic phase for ammonium salts of different constitution and configuration.The influence of concentration of the tartaric acid ester, temperature, concentration and type of the lipophilic anion on Q and P was investigated to find out favourable experimental conditions for resolutions of racemates by iterative processes, e.g. partition chromatography.The relation ship between Q and the configuration of aminoalcohols 1-12 was explored and the observed regularities are pointed out.In addition it was found that lipophilic tartaric acid esters are enantioselective to salts of threo-1,2-diphenyl-1,2-ethanediamine 13, and to phenylglycine and its derivatives 14-16.
- Prelog, Vladimir,Mutak, Stjepan,Kovacevic, Krunoslav
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p. 2279 - 2284
(2007/10/02)
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