- Efficient Synthesis of D-Phenylalanine from L-Phenylalanine via a Tri-Enzymatic Cascade Pathway
-
D-phenylalanine is an important intermediate in food and pharmaceutical industries. Here, to enable efficient D-phenylalanine biosynthesis from L-phenylalanine, a tri-enzymatic cascade was designed and reconstructed in vivo. The activity of Proteus vulgaris meso-diaminopimelate dehydrogenase (PvDAPDH) toward phenyl pyruvic acid was identified as the limiting step. To overcome, the tension in the phenyl pyruvic acid side-chain, PvDAPDH was engineered, generating PvDAPDHW121A/R181S/H227I, whose catalytic activity of 6.86 U mg?1 represented an 85-fold increase over PvDAPDH. Introduction of PvDAPDHW121A/R181S/H227I, P. mirabilis L-amino acid deaminase, and Bacillus megaterium glucose dehydrogenase in E. coli enabled the production of 57.8 g L?1 D-phenylalanine in 30 h, the highest titer to date using 60 g L?1 L-phenylalanine as starting substrate, which meant a 96.3 % conversion rate and >99 % enantioselectivity on a 3-L scale. The proposed tri-enzymatic cascade provides a novel potential bio-based approach for industrial production of D-phenylalanine from cheap amino acids.
- Lu, Cui,Zhang, Sheng,Song, Wei,Liu, Jia,Chen, Xiulai,Liu, Liming,Wu, Jing
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p. 3165 - 3173
(2021/06/09)
-
- Chirality switching in the enantioseparation of 2-hydroxy-4-phenylbutyric acid: Role of solvents in selective crystallization of the diastereomeric salt
-
Chirality switching was induced by solvents in the enantioseparation of 2-hydroxy-4-phenylbutyric acid (HPBA) via diastereomeric salt formation with an enantiopure aminoalcohol. The (S)-salt was crystallized from butanol solutions and the (R)-salt was obt
- Hirose, Takuji,Kodama, Koichi,Shitara, Hiroaki,Yi, Meng
-
-
- Highly Efficient Deracemization of Racemic 2-Hydroxy Acids in a Three-Enzyme Co-Expression System Using a Novel Ketoacid Reductase
-
Enantiopure 2-hydroxy acids (2-HAs) are important intermediates for the synthesis of pharmaceuticals and fine chemicals. Deracemization of racemic 2-HAs into the corresponding single enantiomers represents an economical and highly efficient approach for synthesizing chiral 2-HAs in industry. In this work, a novel ketoacid reductase from Leuconostoc lactis (LlKAR) with higher activity and substrate tolerance towards aromatic α-ketoacids was discovered by genome mining, and then its enzymatic properties were characterized. Accordingly, an engineered Escherichia coli (HADH-LlKAR-GDH) co-expressing 2-hydroxyacid dehydrogenase, LlKAR, and glucose dehydrogenase was constructed for efficient deracemization of racemic 2-HAs. Most of the racemic 2-HAs were deracemized to their (R)-isomers at high yields and enantiomeric purity. In the case of racemic 2-chloromandelic acid, as much as 300 mM of substrate was completely transformed into the optically pure (R)-2-chloromandelic acid (> 99% enantiomeric excess) with a high productivity of 83.8 g L?1 day?1 without addition of exogenous cofactor, which make this novel whole-cell biocatalyst more promising and competitive in practical application.
- Xue, Ya-Ping,Wang, Chuang,Wang, Di-Chen,Liu, Zhi-Qiang,Zheng, Yu-Guo
-
-
- Asymmetric synthesis of (S)-dihydrokavain from l-malic acid
-
A practical and efficient asymmetric synthesis of (S)-dihydrokavain from known ethyl (S)-2-hydroxy-4-phenylbutanoate which is, in turn, readily available from l-malic acid as a cheap chiral pool material is described using regioselective ring-opening of the 1,2-cyclic sulfate with lithium-3,3,3-triethoxypropiolate and subsequent HgO/H2SO4-mediated lactonization as the key steps. Its opposite enantiomer (R)-dihydrokavain was also synthesized from d-malic acid using the same sequences of reactions for the purpose of optical purity determination.
- Eskici, Mustafa,Karanfil, Abdullah,?zer, M. Sabih,Kabak, Yal??n,Durucasu, ?nci
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p. 2382 - 2390
(2018/10/20)
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- Preparation method of (R)-2-hydroxyl-4-phenyl butyric acid
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The invention discloses a preparation method of (R)-2-hydroxyl-4-phenyl butyric acid. The method comprises the following steps: carrying out catalytic reduction on 2-oxo-4-phenyl butyric acid-L-menthyl ester in an alcohol system to obtain (R)-2-hydroxyl-4
- -
-
Paragraph 0023
(2017/07/21)
-
- Chloramphenicol base chemistry. Part 10: Asymmetric synthesis of α-hydroxy chiral alcohols via intramolecular Michael additions of γ-hydroxy-α, β-unsaturated enones with chloramphenicol base derived bifunctional urea organocatalysts
-
We have developed the chloramphenicol base urea-catalyzed intramolecular Michael addition of γ-hydroxy-α, β-unsaturated enones. The oxidation of the resulting products provided facile access to the corresponding α-hydroxy chiral alcohols with good efficiency and enantioselectivity, with the reaction displaying broad substrate scope. The utility of this methodology was further demonstrated by the synthesis of (R)-2-hydroxy-4-phenylbutanoate, which is a key building block for the construction of the ACE inhibitor benazepril hydrochloride.
- Wang, Haifeng,Yan, Linjie,Wu, Yan,Chen, Fener
-
p. 2793 - 2800
(2017/04/14)
-
- Method for preparing lisinopril intermediate
-
The invention provides a method for preparing a lisinopril intermediate. The lisinopril intermediate is (R)-2-hydroxyl-4-phenylbutyrate. The method has the advantages that the lisinopril intermediate is made of inexpensive and easily available raw materials which are benzaldehyde and pyruvic acid, four-step efficient reaction including condensation, biological enzyme catalytic asymmetric reduction, double-bond hydrogenation and esterification is carried out on the benzaldehyde and the pyruvic acid, and accordingly an optically pure target product (R)-HPBE [(R)-2-hydroxyl-4-phenylbutyrate] can be ultimately obtained at the overall yield of 83%.
- -
-
Paragraph 0047; 0051
(2017/04/03)
-
- Asymmetric hydrogenation reaction of alpha-ketoacids compound
-
The invention relates to the technical field of organic chemistry, especially to an asymmetric hydrogenation reaction of an alpha-ketoacids compound. The asymmetric hydrogenation reaction comprises a scheme shown in the description. In the scheme, R1 is phenyl, substituted phenyl, naphthyl, substituted naphthyl, C1-C6 alkyl, or aralkyl; a substituent group is C1-C6 alkyl, C1-C6 alkoxy, or halogen; and the number of the substituent group is 1-3. In the scheme, M is a chiral spiro-pyridylamino phosphine ligand iridium complex having a structure shown in the description. In the structure, R is hydrogen, 3-methyl, 4-tBu, or 6-methyl.
- -
-
Paragraph 0037; 0045
(2016/10/10)
-
- Nitrilases
-
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.
- -
-
Paragraph 0495
(2015/09/22)
-
- Direct asymmetric hydrogenation of α-keto acids by using the highly efficient chiral spiro iridium catalysts
-
A new efficient and highly enantioselective direct asymmetric hydrogenation of α-keto acids employing the Ir/SpiroPAP catalyst under mild reaction conditions has been developed. This method might be feasible for the preparation of a series of chiral α-hydroxy acids on a large scale.
- Yan, Pu-Cha,Xie, Jian-Hua,Zhang, Xiang-Dong,Chen, Kang,Li, Yuan-Qiang,Zhou, Qi-Lin,Che, Da-Qing
-
supporting information
p. 15987 - 15990
(2015/02/19)
-
- One-pot, single-step deracemization of 2-hydroxyacids by tandem biocatalytic oxidation and reduction
-
A facile and efficient one-pot, single-step method for deracemizing a broad range of 2-hydroxyacids to (R)-2-hydroxyacids was established by combination of resting cells of an (S)-hydroxyacid dehydrogenase-producing microorganism and an (R)-ketoacid reductase-producing microorganism.
- Xue, Ya-Ping,Zheng, Yu-Guo,Zhang, Ya-Qin,Sun, Jing-Lei,Liu, Zhi-Qiang,Shen, Yin-Chu
-
supporting information
p. 10706 - 10708
(2013/11/06)
-
- Two-enzyme coexpressed recombinant strain for asymmetric synthesis of ethyl (R)-2-hydroxy-4-phenylbutyrate
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(R)-2-Hydroxy-4-phenylbutyrate (HPBE) is an important chiral intermediate for the synthesis of angiotensin-converting enzyme (ACE) inhibitors. Asymmetric reduction of ethyl 2-oxo-4-phenyl-butyrate (OPBE) to (R)-HPBE using a recombinant strain can provide high enantioselectivity. Cofactor regeneration is a critical issue in the application of a recombinant strain. A carbonyl reductase gene (iolS) and a glucose dehydrogenase (GDH) gene from Bacillus subtilis were cloned. Recombinant IolS was purified using a Ni-NTA column and its enzyme activity properties were investigated. The purified IolS exhibited maximum activity at pH 6.0 and 30°C, and the enzyme showed good thermostability below 40°C. It retained over 75 of its activity in the acidic pH range of 5.5(7.0. Three coexpression strategies were used for the recombinant vectors. The recombinant E. coli strain containing polycistronic plasmid pET-G-T7-I showed excellent carbonyl reductase activity, and the specific activity of both IolS and GDH in the crude cell extract reached 1.5 U/mg. In the asymmetric reduction of OPBE by recombinant E. coli cells in aqueous system, the yield of (R)-HPBE reached over 99 with an enantiomeric excess of 99.5 at 10 g/L of OPBE within 15 h.
- Su, Yuning,Ni, Ye,Wang, Junchao,Xu, Zhihao,Sun, Zhihao
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p. 1650 - 1660
(2013/01/15)
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- Highly enantioselective hydrogenation of 2-oxo-4-arybutanoic acids to 2-hydroxy-4-arylbutanoic acids
-
The Ru-catalyzed asymmetric hydrogenation of 2-oxo-4-arybutanoic acids to afford 2-hydroxy-4-arybutanoic acids was accomplished by employing SunPhos as chiral ligand and 1 M aq HBr as additive. The high enantioselectivities (88.4%-92.6% ee) and efficiency (TON=10,000, TOF=300 h-1) make this method efficient for the synthesis of an important intermediate, (R)-2-hydroxy-4-phenylbutanoic acid, for ACE inhibitors.
- Zhu, Lufeng,Chen, Houhe,Meng, Qinghua,Fan, Weizheng,Xie, Xiaomin,Zhang, Zhaoguo
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supporting information; experimental part
p. 6186 - 6190
(2011/09/19)
-
- Direct asymmetric hydrogenation of 2-oxo-4-arylbut-3-enoic acids
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A challenging direct asymmetric hydrogenation of (E)-2-oxo-4-arylbut-3- enoic acids to give 2-hydroxy-4-arylbutanoic acids (85.4-91.8% ee) was achieved with a Ru catalyst based on SunPhos as the chiral ligand. Further investigation of the reaction revealed that partial isomerization of 2-hydroxy-4-arylbutenoic acids was involved in the hydrogenation process. Employing the reaction conditions to the hydrogenation of 2-oxo-4-phenylbutanoic acid resulted in better enantioselectivity (91.8% ee) and efficiency (TON = 2000, TOF = 200 h-1), which offers a useful method for the synthesis of a common intermediate for ACE inhibitors.
- Zhu, Lvfeng,Meng, Qinghua,Fan, Weizheng,Xie, Xiaomin,Zhang, Zhaoguo
-
supporting information; experimental part
p. 6027 - 6030
(2010/11/18)
-
- A new chemo-enzymatic route to chiral 2-hydroxy-4-phenylbutyrates by combining lactonase-mediated resolution with hydrogenation over Pd/C
-
A new chemo-enzymatic route to both isomers of 2-hydroxy-4-phenylbutyric acid is reported. The key step is the lactonase-catalyzed hydrolysis of cis- and trans-2-hydroxy-4-phenyl-4-butyrolactones followed by hydrogenation over Pd/C to afford optically pure 2-hydroxy-4-phenylbutyric acid.
- Chen, Bing,Yin, Hai-Feng,Wang, Zhen-Sheng,Liu, Jia-Ying,Xu, Jian-He
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supporting information; experimental part
p. 2754 - 2756
(2010/09/04)
-
- Serendipitous discovery of α-hydroxyalkyl esters as β-lactamase substrates
-
O-(1-Carboxy-1-alkyloxycarbonyl) hydroxamates were found to spontaneously decarboxylate in aqueous neutral buffer to form O-(2-hydroxyalkylcarbonyl) hydroxamates. While the former molecules do not react rapidly with serine β-lactamases, the latter are quite good substrates of representative class A and C, but not D, enzymes, and particularly of a class C enzyme. The enzymes catalyze hydrolysis of these compounds to a mixture of the α-hydroxy acid and hydroxamate. Analogous compounds containing aryloxy leaving groups rather that hydroxamates are also substrates. Structure-activity experiments showed that the α-hydroxyl group was required for any substantial substrate activity. Although both d- and l-α-hydroxy acid derivatives were substrates, the former were preferred. The response of the class C activity to pH and to alternative nucleophiles (methanol and d-phenylalanine) suggested that the same active site functional groups participated in catalysis as for classical substrates. Molecular modeling was employed to explore how the α-hydroxy group might interact with the class C β-lactamase active site. Incorporation of the α-hydroxyalkyl moiety into novel inhibitors will be of considerable interest.
- Pelto, Ryan B.,Pratt
-
experimental part
p. 10496 - 10506
(2011/10/18)
-
- Enantioselective organocatalytic rearrangement of α-acyloxy- β-keto sulfides to α-acyloxy thioesters
-
The first highly enantioselective organocatalytic rearrangement of α-acyloxy-β-keto sulfides to α-acyloxy thioesters has been developed which provides a number of important synthetic building blocks in high yield and with excellent enantioselectivities (e
- Capitta, Francesca,Frongia, Angelo,Piras, Pier Paolo,Pitzanti, Patrizia,Secci, Francesco
-
supporting information; experimental part
p. 2955 - 2960
(2011/02/22)
-
- METHOD FOR PRODUCING OPTICALLY ACTIVE HYDROXYCARBOXYLIC ACID DERIVATIVE OR SALT THEREOF
-
The present invention has its object to provide a method for producing an optically active hydroxycarboxylic acid derivative which is an intermediate important for production of medicines, agrochemicals, chemical products, and so on. The production method of the present invention comprises: carrying out a hydrogen-transfer reduction of a ketocarboxylic acid or a salt thereof by the reaction of an optically active diamine complex to produce an optically active hydroxycarboxylic acid derivative. According to the present invention, it is possible to safely and efficiently produce an industrially-useful optically active hydroxycarboxylic acid derivative.
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-
Page/Page column 11-12
(2009/06/27)
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- Design and synthesis of novel 2-pyridone peptidomimetic falcipain 2/3 inhibitors
-
The structure-based design, chemical synthesis and in vitro activity evaluation of various falcipain inhibitors derived from 2-pyridone are reported. These compounds contain a peptidomimetic binding determinant and a Michael acceptor terminal moiety capable of deactivating the cysteine protease active site.
- Verissimo, Edite,Berry, Neil,Gibbons, Peter,Cristiano, M. Lurdes S.,Rosenthal, Philip J.,Gut, Jiri,Ward, Stephen A.,O'Neill, Paul M.
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scheme or table
p. 4210 - 4214
(2009/04/10)
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- Enantio-complementary deracemization of (±)-2-hydroxy-4- phenylbutanoic acid and (±)-3-phenyllactic acid using lipase-catalyzed kinetic resolution combined with biocatalytic racemization
-
Deracemization of (±)-3-phenyllactic acid (1) and (±)-2-hydroxy-4-phenylbutanoic acid (2) was accomplished by lipase-catalysed kinetic resolution coupled to biocatalytic racemization of the non-reacting substrate enantiomers using Lactobacillus paracasei DSM 20008. Cyclic repetition of this sequence led to a single enantiomeric product from the racemate. Access to both enantiomers was achieved by switching between lipase-catalysed acyl-transfer and ester hydrolysis reactions. Both products constitute important building blocks for virus protease- and ACE-inhibitors, respectively.
- Larissegger-Schnell, Barbara,Glueck, Silvia M.,Kroutil, Wolfgang,Faber, Kurt
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p. 2912 - 2916
(2007/10/03)
-
- PROLINE ESTER AND PREPARATION CONTAINING THE SAME FOR PERCUTANEOUS ADMINISTRATION
-
A proline ester represented by the following formula (I) : wherein R1 represents a hydroxy-lower alkyl group, a lower alkoxy-lower alkyl group, or a lower alkoxy-lower alkoxy-lower alkyl group or a pharmaceutically acceptable salt thereof. The
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-
- Biocatalytic racemization of aliphatic, arylaliphatic, and aromatic α-hydroxycarboxylic acids
-
Biocatalytic racemization of a range of aliphatic, (aryl)aliphatic, and aromatic α-hydroxycarboxylic acids was accomplished by using whole resting cells of a range of Lactobacillus spp. The mild (physiological) reaction conditions ensured an essentially "clean" isomerization in the absence of side reactions, such as elimination or decomposition. Whereas straight-chain aliphatic 2-hydroxy-carboxylic acids were racemized with excellent rates (up to 85% relative to lactate), steric hindrance was observed for branched-chain analogues. Good rates were observed for aryl-alkyl derivatives, such as 3-phenyllactic acid (up to 59%) and 4-phenyl-2-hydroxybutanoic acid (up to 47%). In addition, also mandelate and its o-chloro analogue were accepted at a fair rate (45%). This biocatalytic racemization represents an important tool for the deracemization of a number of pharmaceutically important building blocks.
- Glueck, Silvia M.,Pirker, Monika,Nestl, Bettina M.,Ueberbacher, Barbara T.,Larissegger-Schnell, Barbara,Csar, Katrin,Hauer, Bernhard,Stuermer, Rainer,Kroutil, Wolfgang,Faber, Kurt
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p. 4028 - 4032
(2007/10/03)
-
- Chemo-enzymatic synthesis of (R)-and (S)-2-hydroxy-4-phenylbutanoic acid via enantio-complementary deracemization of (±)-2-hydroxy-4-phenyl-3- butenoic acid using a racemase-lipase two-enzyme system
-
Deracemization of (±)-2-hydroxy-4-phenylbut-3-enoic acid was accomplished by lipase-catalyzed kinetic resolution coupled to mandelate racemase-mediated racemization of the non-reacting substrate enantiomer. Stepwise cyclic repetition of this sequence led
- Larissegger-Schnell, Barbara,Kroutil, Wolfgang,Faber, Kurt
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p. 1936 - 1938
(2007/10/03)
-
- Biocatalytic racemisation of α-hydroxycarboxylic acids at physiological conditions
-
Biocatalytic racemisation of aliphatic, aryl-aliphatic and aromatic α-hydroxycarboxylic acids was accomplished using whole resting cells of Lactobacillus paracasei DSM 20207; the mild (physiological) reaction conditions ensured an essentially 'clean' isomerization in the absence of side reactions, such as elimination or decomposition. The Royal Society of Chemistry 2005.
- Glueck, Silvia M.,Larissegger-Schnell, Barbara,Csar, Katrin,Kroutil, Wolfgang,Faber, Kurt
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p. 1904 - 1905
(2007/10/03)
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- Evaluation of the lipase from Bacillus thermocatenulatus as an enantioselective biocatalyst
-
The lipase from Bacillus thermocatenulatus (BTL2) has been immobilized using different techniques, and used in the resolution of different chiral substrates in hydrolytic reactions. This enzyme acts as an interesting biocatalyst for these types of reactio
- Palomo, Jose M.,Fernandez-Lorente, Gloria,Rua, Maria L.,Guisan, Jose M.,Fernandez-Lafuente, Roberto
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p. 3679 - 3687
(2007/10/03)
-
- Heterogeneous Enantioselective Hydrogenation of Activated Ketones Catalyzed by Modified Pt-Catalysts: A Systematic Structure-Selectivity Study
-
A systematic structure-selectivity study was carried out for the enantioselective hydrogenation of activated ketones with chirally modified Pt/Al2O3 catalysts. For this, 18 modifiers containing an extended aromatic system able to form a strong adsorption complex with the Pt surface, and a suitable chiral group with an amino function capable to interact with the keto group of the substrate (HCd, Qd, HCn, Qn, and semi-synthetic derivatives, as well as synthetic analogues) were prepared and tested on 8 different activated ketones in AcOH and toluene under standard conditions. It was found that relatively small structural changes of the substrate and/or modifier structures strongly affected the enantioselectivity, and that no "best" modifier exists for all substrates. The highest ees for all substrates were obtained with quinuclidine-derived modifiers in combination with naphthalene or quinoline rings, either in AcOH (substrates 1-5 and 8, all carrying an sp3 carbon next to the keto group) or toluene (6 and 7, with an sp2 carbon next to the ketone). The presence and nature of the substituent R′ at the quinuclidine significantly affected the ee (positive and negative effects). Certain combinations of an aromatic system and an amino function were preferred: For the quinuclidine moiety, quinoline and to a somewhat lesser extent naphthalene were a better match, while for the pyrrolidinylmethyl group anthracene was better suited. Methylation of the OH group often had a positive effect for hydrogenations in AcOH but not in toluene. With the exception of 8, higher ees were obtained for the Cd/ Qn series [leading to (R)-products] than for the Cn/ Qd series [leading to (S)-products]. In several cases, opposite structure-selectivity trends were detected when comparing reactions in toluene and AcOH, indicating a significant influence of the solvent.
- Exner, Christian,Pfaltz, Andreas,Studer, Martin,Blaser, Hans-Ulrich
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p. 1253 - 1260
(2007/10/03)
-
- (S)-3-methyl-2-phenylbutylamine, a versatile agent to resolve chiral, racemic carboxylic acids
-
(S)-Ibuprofen 2, (S)-ketoprofen 3, and (S)-naproxen 4 are all obtained by optical resolution of the respective racemates with (S)-3-methyl-2-phenylbutylamine (PBA) 1: (S)-2, 98.7% ee, 39.8% yield; (S)-3, 99.4% ee, 36.7% yield; (S)-4, 99.2% ee, 35.1% yield. (S)-PBA 1 is also useful in resolving other racemic carboxylic acids of pharmaceutical importance; (R)-2-hydroxy-4-phenylbutanoic acid (HPBA) 5, a key intermediate for ACE inhibitors such as benazapril 7, and (S)-2-benzylsuccinic acid (BSA) 6, a key intermediate for hypoglycemic KAD-1229 8, are obtained in 99% ee and 34.4% yield, and in 99% ee and 32.2% yield, respectively.
- Chikusa, Yasuo,Fujimoto, Taizo,Ikunaka, Masaya,Inoue, Toru,Kamiyama, Shunji,Maruo, Koichi,Matsumoto, Jun,Matsuyama, Keisuke,Moriwaki, Masafumi,Nohira, Hiroyuki,Saijo, Shigeya,Yamanishi, Masato,Yoshida, Kazuto
-
p. 291 - 296
(2013/09/06)
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- Dynamic kinetic resolution via dual-function catalysis of modified cinchona alkaloids: Asymmetric synthesis of α-hydroxy carboxylic acids
-
A highly enantioselective catalytic transformation of racemic α-hydroxy acids to optically active α-hydroxy acids is reported. A new procedure was developed for the condensation of racemic α-hydroxy acids with trichloromethyl chloroformate (diphosgene) at room temperature in the presence of activated charcoal to form 5-substituted-1,3-dioxolane-2,4-diones in 90-100% yield. An efficient dynamic kinetic resolution of 5-aryl dioxolanediones was realized via a modified cinchona alkaloid-catalyzed alcoholytic opening of the dioxolanedione ring, generating a variety of optically active α-hydroxy esters in 91-96% ee and 61-85% chemical yield. In this dynamic kinetic resolution, the modified cinchona alkaloid was found to serve dual catalytic roles, mediating both the rapid racemization of the 5-aryl dioxolanediones and the enantioselective alcoholytic ring opening of the 5-aryl dioxolanediones. Consequently, both enantiomers of the 5-aryl dioxolanediones were converted to highly enantiomerically enriched aromatic α-hydroxy esters in yields (61-85%), far exceeding the maximum of 50% for a normal kinetic resolution. This development not only represents an expansion of the scope of asymmetric acyl-transfer catalysis of synthetic catalysts but also provides a new approach for the development of efficient chemical dynamic kinetic resolutions promoted by a single catalyst. 5-Alkyl dioxolanediones were resolved by a conventional but highly enantioselective kinetic resolution to provide α-hydroxy acids and esters in high optical purity and good yields. Copyright
- Tang, Liang,Deng, Li
-
p. 2870 - 2871
(2007/10/03)
-
- Efflux pump inhibitors
-
Compounds are described which have efflux pump inhibitor activity. Also described are methods of using such efflux pump inhibitor compounds and pharmaceutical compositions which include such compounds.
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-
- Process for producing optically active 2-hydroxy-4-arylbutyric acid or its ester
-
Provided is an industrially useful process for producing an optically active 2-hydroxy-4-arylbutyric acid or its ester. An optically active acyloxysuccinic anhydride is reacted with an aromatic compound in the presence of a Lewis acid to produce an optically active 2-acyloxy-4-oxo-4-arylbutyric acid. The 2-acyloxy-4-oxo-4-arylbutyric acid is converted to an optically active 2-acyloxy-4-arylbutyric acid through catalytic reduction. The 2-acyloxy-4-arylbutyric acid is hydrolyzed in the presence of an acid or an alkali to produce an optically active 2-hydroxy-4-arylbutyric acid. The 2-hydroxy-4-arylbutyric acid is reacted with an alcohol in the presence of an acid to produce an optically active 2-hydroxy-4-arylbutyric acid ester.
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-
- Facile synthesis of (S)-β-hydroxy-β-trichloromethylated aromatic ketones by the regioselective ring cleavage of chiral β-trichloromethyl-β-propiolactone under the Friedel-Crafts conditions
-
The reaction of enantiomerically pure β-trichloromethyl-β-propiolactone (1) as a chiral building block with an aromatic compound in the presence of Lewis acid provided an acylated product with a chiral trichloromethyl carbinol moiety. The acylated product was used as an effective chiral synthon for natural product synthesis such as enalapril of ACE inhibitor.
- Fujisawa, Tamotsu,Ito, Takatoshi,Fujimoto, Kenji,Shimizu, Makoto,Wynberg,Staring
-
p. 1593 - 1596
(2007/10/03)
-
- Microbial reduction of 2-oxo-4-phenylbutyric acid and its ester
-
Stereoselectivity of microbial reduction of 2-oxo-4-phenylbutyric acid and corresponding ethyl ester have been studied. A number of microorganisms capable of reduction of the acid with high R-selectivity have been identified and conditions for preparative
- Kruszewska,Makuch,Grynkiewicz,Cybulski
-
p. 1301 - 1307
(2007/10/03)
-
- Enzymatic resolution of 2-hydroxy-4-phenylbutanoic acid and 2-hydroxy-4-phenylbutenoic acid
-
Racemic 2-hydroxy-4-phenylbutanoic acid and 2-hydroxy-4-phenyl-butenoic acid have been resolved using a lipase. In each case, the (R)-2-hydroxy and the (S)-2-acetoxy acids were isolated with high enantiomeric excess and yield.
- Chadha,Manohar
-
p. 651 - 652
(2007/10/02)
-
- A Novel Highly Diastereoselective Synthesis of Cyano Esters by Regioselective Ring Opening of Chiral Oxazolidinium Methiodides with Sodium Cyanide
-
Sodium cyanide reacts with chiral oxazolidinium methiodides, prepared by quaternization of oxazolidines with methyl iodide, leading regio- and stereoselectively (d.e. 82-94percent) to cyano esters in moderate to good chemical yields (51-95percent).The open compounds are isolated as a pure diastereomer by a single recrystallization of their ammonium methiodides, and converted into enantiomerically pure α-hydroxy acids by heating with a concentrated solution of hydrochloric acid. - Key words: Chiral Oxazolidinium Iodides; alpha-Cyano ethers, Diastereoselective Ring Opening; alpha-Hydroxy Acids; Asymmetric Synthesis.
- Andres, Celia,Delgado, Manuel,Pedrosa, Rafael,Rodriquez, Raquel
-
p. 8325 - 8328
(2007/10/02)
-
- Process for making and isolating (R)-2-hydroxy-4-phenylbutyric acid and esters
-
Disclosed herein is a novel compound, (L)-menthyl 2-oxo-4-phenylbutyrate, and an improved process for making and isolating a substantially pure compound of the structural formula: STR1 wherein Y is hydrogen or (L)-menthyl the improvement which comprises: (a) stereoselectively reducing (L)-menthyl 2-oxo-4-phenylbutyrate by contacting said compound with S-B-(3-pinanyl)-9 horabicyclo[3,3,1]nonone, (b) stereoselectively isolating (L)-menthyl-(R)-2-hydroxy-4-phenylbutyrate by crystallization, and optionally hydrolyzing the so obtained ester; and further comprises optionally esterifying the so obtained acid by contacting said acid with a C1 -C6 alkanol in presence of acid.
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-
- Asymmetric Hydrocyanation of Aldehydes Using Chiral Titanium Reagents
-
Two highly enantioselective methods for hydrocyanation of aldehydes were developed by using chiral alkoxytitanium reagents.Treatment of benzaldehyde with cyanotrimethylsilane in the presence of a chiral alkoxytitanium affords mandelonitrile in good chemic
- Minamikawa, Hiroyuki,Hayakawa, Satoshi,Yamada, Tohru,Iwasawa, Nobuharu,Narasaka, Koichi
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p. 4379 - 4384
(2007/10/02)
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- Angiotensin-Converting Enzyme Inhibitors: Perhydro-1,4-thiazepin-5-one Derivatives
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α-amino>-5-oxoperhydro-1,4-thiazepin-4-yl>acetic acids (monoester monoacids) and their dicarboxylic acids having the hydrophobic substituents at the 2- or 3-position of the thiazepinone ring were prepared and assayed for angiotensin-converting enzyme (ACE) inhibitory activity.The dicarboxylic acids having the pseudoequatorial amino groups at the 6-position and the pseudoequatorial hydrophobic substituents at the 2- or 3-position of the chair conformation of the thiazepinone ring had potent in vitro inhibitory activity.The monoester monoacids having the hydrophobic substituents at the 2-position suppressed pressor response to angiotensin I for a longer duration than those having the substituents at the 3-position when administered orally.The structure-activity relationship was studied by conformational energy calculations of the thiazepinone ring.
- Yanagisawa, Hiroaki,Ishihara, Sadao,Ando, Akiko,Kanazaki, Takuro,Miyamoto, Shuichi,et al.
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p. 1984 - 1991
(2007/10/02)
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