- Dutch resolution of racemic 4-hydroxy- and 4-fluorophenylglycine with mixtures of phenylglycine and (+)-10-camphorsulfonic acid
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4-Hydroxyphenylglycine and 4-fluorophenylglycine can be resolved with (+)-10-camphorsulfonic acid only if DL- or D-(-)-phenylglycine is added. When using DL-phenylglycine this is co-resolved in this process. In this resolution process mixed crystals are formed of the (+)-10-camphorsulfonic acid salts of the D-(-)-enantiomers of phenylglycine and the para substituted phenylglycines. In the crystal lattice of the mixed salts approximately 25- 30% of the D-(-)-phenylglycine molecules can be randomly replaced by D-(-)- para substituted phenylglycines, resulting in the desired resolution. The overall non-stoichiometric composition of the mixed crystals reflects to some extent the composition in solution. This behaviour is typical for solid solutions. The solid solution behaviour in this so called 'Dutch resolution' is proven by differential scanning calorimetry (DSC), X-ray crystal structure determination and powder diffraction. (C) 2000 Elsevier Science Ltd.
- Kaptein, Bernard,Elsenberg, Henk,Grimbergen, Reinier F. P.,Broxterman, Quirinus B.,Hulshof, Lumbertus A.,Pouwer, Kees L.,Vries, Ton R.
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Read Online
- Efficient chemoenzymatic synthesis of (S)-α-amino-4-fluorobenzeneacetic acid using immobilized penicillin amidase
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An efficient chemoenzymatic route was developed for synthesis of (S)-α-amino-4-fluorobenzeneacetic acid, a valuable chiral intermediate of Aprepitant, using immobilized penicillin amidase catalyzed kinetic resolution of racemic N-phenylacetyl-4-fluorophen
- Lin, Chao-Ping,Tang, Xiao-Ling,Zheng, Ren-Chao,Zheng, Yu-Guo
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Read Online
- Synthesis of Air- and Moisture-Stable, Storable Chiral Oxorhenium Complexes and Their Application as Catalysts for the Enantioselective Imine Reduction
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Air-/moisture-stable, crystalline, and storable chiral salicyloxazoline based oxorhenium(V) complexes have been synthesized and their catalytic application for the asymmetric reduction of ketimines using hydrosilane as hydride source is disclosed. A broad substrate scope, high yields, and excellent enantioselectivities (up to 99 %) are attained. Furthermore, the syntheses of enantiopure α-amino esters, γ- and δ-lactams, and isoindolinones have also been carried out using this methodology. Finally, the method has been applied to synthetic targets of pharmaceutical relevance, such as R-(+)-salsolidine and R-(+)-crispine A.
- Das, Braja Gopal,Nallagonda, Rajender,Dey, Dhananjay,Ghorai, Prasanta
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p. 12601 - 12605
(2015/09/01)
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- Nitrilases
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The invention relates to nitrilases and to nucleic acids encoding the nitrilases. In addition, methods of designing new nitrilases and methods of use thereof are also provided. The nitrilases have increased activity and stability at increased pH and temperature.
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Paragraph 0495
(2015/09/22)
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- Enzymatic synthesis of chiral phenylalanine derivatives by a dynamic kinetic resolution of corresponding amide and nitrile substrates with a multi-enzyme system
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Mutant α-amino-ε-caprolactam (ACL) racemase (L19V/L78T) from Achromobacter obae with improved substrate specificity toward phenylalaninamide was obtained by directed evolution. The mutant ACL racemase and thermostable mutant D-amino acid amidase (DaaA) from Ochrobactrum anthropi SV3 co-expressed in Escherichia coli (pACLmut/pDBFB40) were utilized for synthesis of (R)-phenylalanine and non-natural (R)-phenylalanine derivatives (4-OH, 4-F, 3-F, and 2-F-Phe) by dynamic kinetic resolution (DKR). Recombinant E. coli with DaaA and mutant ACL racemase genes catalyzed the synthesis of (R)-phenylalanine with 84% yield and 99% ee from (RS)-phenylalaninamide (400 mM) in 22 h. (R)-Tyrosine and 4-fluoro-(R)-phenylalanine were also efficiently synthesized from the corresponding amide compounds. We also co-expresed two genes encoding mutant ACL racemase and L-amino acid amidase from Brevundimonas diminuta in E. coli and performed the efficient production of various (S)-phenylalanine derivatives. Moreover, 2-aminophenylpropionitrile was converted to (R)-phenylalanine by DKR using a combination of the non-stereoselective nitrile hydratase from recombinamt E. coli and mutant ACL racemase and DaaA from E. coli encoding mutant ACL racemase and DaaA genes. Copyright
- Yasukawa, Kazuyuki,Asano, Yasuhisa
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p. 3327 - 3332
(2013/01/15)
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- A remarkable titanium-catalyzed asymmetric strecker reaction using hydrogen cyanide at room temperature
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Close to perfect enantioselectivity (up to 98% ee) is obtained for the formation of amino nitrites using hydrogen cyanide (HCN) as the cyanide source at room temperature for the first time. In an operationally simple process, the catalyst generated from a partially hydrolyzed titanium alkoxide (PHTA) and (S)-N-salicyl-ss-amino alcohol ligand, catalyzes the cyanation of imines in a short reaction time.
- Ramalingam, Balamurugan,Seayad, Abdul Majeed,Chuanzhao, Li,Garland, Marc,Yoshinaga, Kazuhiko,Wadamoto, Manabu,Nagata, Takushi,Chai, Christina L. L.
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supporting information; scheme or table
p. 2153 - 2158
(2010/11/04)
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- Chemoenzymatic approaches to the dynamic kinetic asymmetric synthesis of aromatic amino acids
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Enzymatic approaches for the production of amino acids by nitrilases are described. Dynamic kinetic asymmetric synthesis conditions were established for the aromatic aminonitriles, phenylglycinonitrile and 4- fluorophenylglycinonitrile, at high pH to produce the corresponding amino acid products in high enantiomeric excess. N-Acylation of aromatic aminonitriles led to spontaneous racemization at pH 8, allowing preferential enzymatic hydrolysis of the (R)-enantiomer to afford the product N-acylamino acids in up to 99% enantiomeric excess (ee).
- Chaplin, Jennifer A.,Levin, Michael D.,Morgan, Brian,Farid, Nancy,Li, Jen,Zhu, Zuolin,McQuaid, Jeff,Nicholson, Lawrence W.,Rand, Cynthia A.,Burk, Mark J.
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p. 2793 - 2796
(2007/10/03)
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- A practical asymmetric synthesis of homochiral α-arylglycines
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Enantioselective reduction of a series of substituted aryl trichloromethyl ketones with the CBS-catecholborane reagent afforded homochiral aryl trichloromethyl carbinols which have been elaborated to give homochiral α-arylglycines in high e.e.
- Mellin-Morliere, Christelle,Aitken, David J.,Bull, Steven D.,Davies, Stephen G.,Husson, Henri-Philippe
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p. 149 - 155
(2007/10/03)
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- Polymorphic form of a tachykinin receptor antagonist
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This invention is concerned with a novel polymorphic form of the compound 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-phenyl)-ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine which is a tachykinin receptor antagonist useful in the treatment or prevention of disorders of the central nervous system, inflammatory diseases, pain or migraine, asthma, and emesis. The instant polymorphic form has advantages over the other known forms of 2-(R)-(1-(R)-(3,5-bis(trifluoro-methyl)-phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine in terms of thermodynamic stability and suitability for inclusion in pharmaceutical formulations.
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- MORPHOLINE AND THIOMORPHOLINE TACHYKININ RECEPTOR ANTAGONISTS
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Substituted heterocycles of the general structural formula: STR1 are tachykinin receptor antagonists useful in the treatment of inflammatory diseases, pain or migraine, asthma and emesis, and calcium channel blockers useful in the treatment of cardiovascular conditions such as angina, hypertension or ischemia.
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- Efficient chemoenzymatic synthesis of enantiomerically pure α-amino acids
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A general two-step chemoenzymatic synthesis for enantiomerically pure natural and nonnatural α-amino acids is presented. In the first step of the sequence, the ubiquitous educts aldehyde, amide and carbon monoxide react by palladium-catalyzed amidocarbonylation to afford the racemic N-acyl amino acids in excellent yields. In the second step, enzymatic enantioselective hydrolysis yields the free optically pure a-amino acid and the other enantiomer as the N-acyl derivative, both in optical purities of 85-99.5% ee. The advantage of the chemoenzymatic process compared to other amino acid synthesis are demonstrated by the preparation of various functionalized (-OR, -Cl, -F, -SR) α-amino acids on a 10-g scale.
- Beller, Matthias,Eckert, Markus,Geissler, Holger,Napierski, Bernd,Rebenstock, Heinz-Peter,Holla, E. Wolfgang
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p. 935 - 941
(2007/10/03)
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- Syntheses of optically active α-amino nitrites by asymmetric transformation of the second kind using a principle of O. Dimroth
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A mixture of solids As and Bs in equilibrium with the dissolved compounds A1 and B1 is transformed completely into one pure solid, say Bs, if the dissolved compounds A1?B1 are equilibrating in solution. This is applied to transform 1:1 mixtures of solid diastereomeric amygdalates (2-hydroxy-2-phenylacetates; mandelates) (R,R)-3 + (S,R)-3 prepared from racemic α-amino nitriles (R,S)-1 with (R)-mandelic acid 2 into stereochemically pure single diastereomers (R,R)-3, or (S,R)-3 (de > 97%) ('asymmetric transformation of the second kind by application of Dimroth's principle'). Decomposition of the amygdalates (R,R)-3, or (S,R)-3, with aqueous base affords the enantiomerically pure α-amino nitriles (A)-1, or (S)-1 (ten examples). The chiral auxiliary (R)-mandelic acid is recovered almost quantitatively. The optically active α-amino nitriles are hydrolyzed to amides 6, and further to α-N-alkylamino acids 7. N-Benzylamino acids 7 are hydrogenated to α-amino acids 8. Some of the optically active α-amino nitriles 1 are reduced to optically active 1,2-diamines 9. In most cases, absolute configurations could be assigned by comparison of the specific rotations observed with those of authentic compounds.
- Hassan, Nasser A.,Bayer, Erwin,Jochims, Johannes C.
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p. 3747 - 3757
(2007/10/03)
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- MORPHOLINE AND THIOMORPHOLINE TACHYKININ RECEPTOR ANTAGONISTS
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Substituted heterocycles of the general structural formula: STR1 are tachykinin receptor antagonists useful in the treatment of inflammatory diseases, pain or migraine, asthma and emesis, and calcium channel blockers useful in the treatment of cardiovascular conditions such as angina, hypertension or ischemia.
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- Palladium-catalysed asymmetric allylic substitution: Synthesis of α- and β-amino acids
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Methodology has been established for the formation of enantiomerically enriched α-amino acids using palladium-catalysed allylic amination. The formation of enantiomerically enriched allylamines has been achieved with high enantioselectivity. Oxidative cleavage of the allylamines provides arylglycine and glutamic acid derivatives. Additionally, enantiomerically enriched β-amino acids have been prepared in high enantiomeric excess. Palladium-catalysed asymmetric allylic substitution is used as the key synthetic transformation.
- Bower, Justin F.,Jumnah, Roshan,Williams, Andrew C.,Williams, Jonathan M. J.
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p. 1411 - 1420
(2007/10/03)
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- MORPHOLINE COMPOUNDS ARE PRODRUGS USEFUL AS TACHYKININ RECEPTOR ANTAGONISTS
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Substituted heterocycles of the general structural formula: STR1 are tachykinin receptor antagonists useful in the treatment of inflammatory diseases, pain or migraine, asthma, and emesis.
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- Crystallisation induced resolution of 4-fluorophenylglycine
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4-Fluorophenylglycine 1 is resolved to 99.0% e.e. and 65% overall yield via its methyl ester 2 using a crystallisation induced resolution.
- Moseley, Jonathan D.,Williams, Brian J.,Owen, Simon N.,Verrier, Hugh M.
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p. 3351 - 3352
(2007/10/03)
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- HOMOCHIRAL HETEROORGANIC ANALOGS OF NATURAL COMPOUNDS. I. PREPARATIVE BIOCATALYTIC METHOD OF OBTAINING FLUORINE-CONTAINING L- AND D-PHENYLGLYCINES
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A biocatalytic method of obtaining homochiral o- and p-fluorine-substituted phenylglycines by enantiomeric hydrolysis from N-phenylacetyl or N-acetyl derivatives under the action of Escherichia coli penicillin acylase or Streptoverticillium olivoreticuli aminoacylase is proposed.The L form of the amino acid and the unhydrolyzed D-enantiomer of the initial derivative are separated by extraction and chromatographic methods.The acid hydrolysis of the D-enantiomers of N-phenylacetyl derivatives of fluorine-substituted phenylglycines leads to partial (about 15percent) racemization.With a substantially higher (by two orders of magnitude) concentration of enzyme and an increase in the reaction time it is possible to use penicillinase as a catalyst for the hydrolysis of the D-enantiomer of the N-phenylacetyl derivative not accompanied by any appreciable racemization whatever.
- Soloshonok, V. A.,Galaev, I. Yu.,Shvyadas, V. K.,Kozlova, E. V.,Kotik, N. V.,et al.
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p. 228 - 232
(2007/10/02)
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- Synthesis of Optically Active Arylglycines by Photolysis of Optically Active (β-Hydroxyamino) Carbene-Chromium(0) Complexes
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Photolysis of chromium complexes having the optically active amino alcohol (1R,2S)-(-)- or (1S,2R)-(+)-2-amino-1,2-diphenylethanol as the amino group produced aryl-substituted oxazinones in good yield with reasonable diastereoselectivity.Facile separation of diastereoisomers followed by mild reductive cleavage produced several arylglycines, having either electron-donating or withdrawing groups on the aromatic ring, in good overall yield and with excellent enantiomeric excess.
- Vernier, Jean-Michel,Hegedus, Louis S.,Miller, David B.
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p. 6914 - 6920
(2007/10/02)
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- An Efficient and Practical Synthesis of L-α-Amino Acids Using (R)-Phenylglycinol as a Chiral Auxiliary
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L-α-Amino acids including L-α-arylglycines were conveniently and stereoselectively synthesized via the α-amino carbonitriles given by the Strecker reaction of (R)-2-amino-2-phenylethanol with aldehydes and hydrogen cyanide.The stereoselectivity of these α-amino carbonitriles was thermodynamically controlled.
- Inaba, Takashi,Kozono, Ichiro,Fujita, Makoto,Ogura, Katsuyuki
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p. 2359 - 2365
(2007/10/02)
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