- Preparation methods of beta-azido acid and beta-amino acid compounds and application thereof
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The invention discloses a preparation method of beta-azido acid, which comprises the following step of: carrying out a reaction on an ethylene compound, CZ1Z2Z3Z4 and trimethylsilyl azide as initial raw materials to obtain the beta-azido acid. The ethylene compound has a structural general formula as shown in a formula I, and the beta-azido acid has a structural general formula as shown in a formula II, wherein R is selected from one of alkyl, substituted alkyl, heteroaryl and substituted heteroaryl; and Z1, Z2, Z3 and Z4 are respectively and independently at least one selected from fluorine, chlorine, bromine and iodine. The invention further provides beta-amino acid and application of the preparation method. The preparation methods of the beta-azido acid and the beta-amino acid, provided by the invention, have the advantages of cheap raw materials and catalysts, mild reaction conditions, simplicity in operation, high reaction efficiency and the like.
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- Glutamate as an Efficient Amine Donor for the Synthesis of Chiral β- and γ-Amino Acids Using Transaminase
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A recyclable glutamate amine donor system employing transaminase (TA), glutamate dehydrogenase (GluDH) and mutant formate dehydrogenase (FDHm) was developed, wherein amine donor Glu was regenerated using GluDH and thereby circumvented the inhibition of TA by α-ketoglutarate. Various enantiopure β-, γ-amino acids, and amines were successfully synthesized with high conversions and excellent enantiomeric excess using this system.
- Kim, Geon-Hee,Jeon, Hyunwoo,Khobragade, Taresh P.,Patil, Mahesh D.,Sung, Sihyong,Yoon, Sanghan,Won, Yumi,Sarak, Sharad,Yun, Hyungdon
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p. 1437 - 1440
(2019/02/06)
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- Β-phenylalanine ester synthesis from stable β-keto ester substrate using engineered ω-transaminases
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The successful synthesis of chiral amines from ketones using ω-transaminases has been shown in many cases in the last two decades. In contrast, the amination of β-keto acids is a special and relatively new challenge, as they decompose easily in aqueous solution. To avoid this, transamination of the more stable β-keto esters would be an interesting alternative. For this reason, ω-transaminases were tested in this study, which enabled the transamination of the β-keto ester substrate ethyl benzoylacetate. Therefore, a ω-transaminase library was screened using a coloring o-xylylenediamine assay. The ω-transaminase mutants 3FCR_4M and ATA117 11Rd show great potential for further engineering experiments aiming at the synthesis of chiral (S)- and (R)-β-phenylalanine esters. This alternative approach resulted in the conversion of 32% and 13% for the (S)- and (R)-enantiomer, respectively. Furthermore, the (S)-β-phenylalanine ethyl ester was isolated by performing a semi-preparative synthesis.
- BuΒ, Oliver,Voss, Moritz,Delavault, André,Gorenflo, Pascal,Syldatk, Christoph,Bornscheuer, Uwe,Rudat, Jens
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- Characterization of a new nitrilase from Hoeflea phototrophica DFL-43 for a two-step one-pot synthesis of (S)-β-amino acids
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A nitrilase from Hoeflea phototrophica DFL-43 (HpN) demonstrating excellent catalytic activity towards benzoylacetonitrile was identified from a nitrilase tool-box, which was developed previously in our laboratory for (R)-o-chloromandelic acid synthesis from o-chloromandelonitrile. The HpN was overexpressed in Escherichia coli BL21 (DE3), purified to homogeneity by nickel column affinity chromatography, and its biochemical properties were studied. The HpN was very stable at 30–40?°C, and highly active over a wide range of pH values (pH 6.0–10.0). In addition, the HpN could tolerate against several hydrophilic organic solvents. Steady-state kinetics indicated that HpN was highly active towards benzoylacetonitrile, giving a KM of 4.2?mM and a kcat of 170?s?1, the latter of which is ca. fivefold higher than the highest record reported so far. A cascade reaction for the synthesis of optically pure (S)-β-phenylalanine from benzoylacetonitrile was developed by coupling HpN with an ω-transaminase from Polaromonas sp. JS666 in toluene-water biphasic reaction system using β-alanine as an amino donor. Various (S)-β-amino acids could be produced from benzoylacetonitrile derivatives with moderate to high conversions (73–99%) and excellent enantioselectivity (> 99% ee). These results are significantly advantageous over previous studies, indicating a great potential of this cascade reaction for the practical synthesis of (S)-β-phenylalanine in the future.
- Zhang, Zhi-Jun,Cai, Rui-Feng,Xu, Jian-He
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p. 6047 - 6056
(2018/05/15)
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- Synthetic method for novel chiral ligand, metal chelate, multiple unnatural amino acids, maraviroc and key intermediate thereof
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The invention discloses a synthetic method for a novel chiral ligand, a metal chelate, multiple unnatural amino acids, maraviroc and a key intermediate thereof. According to the synthetic method, (R)-2-methylproline is selected as a starting material, and asymmetrical resolution is induced by utilizing a nickel chelate, so that (S)-beta3-amino acid is obtained, and (S)-3-amino-3-phenylpropionic acid is taken as the key intermediate for synthesizing maraviroc, so that yield is high, and ee value reaches more than or equal to 98.2%. The method disclosed by the invention has the advantages that source of raw materials is wide, conditions of a synthetic process are mild, control is easy, and optical purity of products is high.
- -
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Paragraph 0490-0492
(2018/04/26)
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- Configurationally Stable (S)- and (R)-α-Methylproline-Derived Ligands for the Direct Chemical Resolution of Free Unprotected β3-Amino Acids
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Reported herein is a chemical method for the direct resolution of unprotected racemic β-substituted-β-amino acids (β3-AAs) that uses specially designed, stable, and recyclable α-methylproline-derived chiral ligands. The versatility of this methodology is unmatched by biocatalytic approaches. The method shows a broad synthetic generality for various aryl- or alkyl-substituted β3-AAs, and the new nonracemizable ligands can be accessed readily. Furthermore, the presented method produces an excellent stereochemical outcome and has a fully recyclable source of chirality, and the reaction conditions are operationally simple and convenient. The procedure has also been successfully applied to the scalable synthesis of the anti-HIV drug maraviroc.
- Zhou, Shengbin,Wang, Shuni,Wang, Jiang,Nian, Yong,Peng, Panfeng,Soloshonok, Vadim A.,Liu, Hong
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p. 1821 - 1832
(2018/04/27)
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- Chiral synthesis method for chiral beta-amino acid and synthesis method for medicinal intermediate
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The invention relates to a chiral synthesis method for chiral beta-amino acid. The chiral synthesis method comprises the following steps: reacting a compound shown in formula (II) with an acylation reagent to prepare anhydride intermediate reaction liquid under the action of alkali; adding Meldrum's acid into the anhydride intermediate reaction liquid, and performing reaction to generate a compound shown in formula (III); reacting the compound shown in formula (III) with a compound shown in formula (IV) to generate a compound shown in formula (V); reducing the compound shown in formula (V) to generate a compound shown in formula (VI); performing acidic hydrolysis on the compound shown in formula (VI) to generate a compound shown in formula (I), i.e., the chiral beta-amino acid. The chiral synthesis method has the advantages of convenience for synthesis, low cost and simple process, and compared with a disclosed preparation method, is more suitable for industrial production.
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Paragraph 0093; 0094; 0095; 0096
(2018/01/11)
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- A process for preparing S or R-type optical isomer 3 - amino - 3 - phenyl propionic acid
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The invention discloses a method for preparing an S or R type optical isomer 3-amino-3-phenyl propionic acid, wherein R or S represents a chiral center configuration. The method includes the steps: 1) preparing an S or R type optical isomer 3-amino-3-phenyl propionic acid camphor sulfonic acid double salt; 2) carrying out free hydrolysis; after carrying out acid or alkali free hydrolysis of the S or R type optical isomer 3-amino-3-phenyl propionic acid camphor sulfonic acid double salt, filtering to obtain the S or R type optical isomer 3-amino-3-phenyl propionic acid. Used raw material and a split reagent are low in price and easy to obtain, a chiral induction body can be used repeatedly, three wastes are few, moreover, the three processes are greatly simplified, and the method can simultaneously obtain the S or R type optical isomer compound, and is low in cost and suitable for industrialized production.
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Paragraph 0049-0055; 0056-0062
(2017/12/27)
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- Kinetic Resolution of Aromatic β-Amino Acids Using a Combination of Phenylalanine Ammonia Lyase and Aminomutase Biocatalysts
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An enzymatic strategy for the preparation of (R)-β-arylalanines employing phenylalanine aminomutase and ammonia lyase (PAM and PAL) enzymes has been demonstrated. Candidate PAMs with the desired (S)-selectivity from Streptomyces maritimus (EncP) and Bacillus sp. (PabH) were identified via sequence analysis using a well-studied template sequence. The newly discovered PabH could be linked to the first ever proposed biosynthesis of pyloricidin-like secondary metabolites and was shown to display better β-lyase activity in many cases. In spite of this, a method combining the higher conversion of EncP with a strict α-lyase from Anabaena variabilis (AvPAL) was found to be more amenable, allowing kinetic resolution of five racemic substrates and a preparative-scale reaction with >98% (R) enantiomeric excess. This work represents an improved and enantiocomplementary method to existing biocatalytic strategies, allowing simple product separation and modular telescopic combination with a preceding chemical step using an achiral aldehyde as starting material. (Figure presented.).
- Weise, Nicholas J.,Ahmed, Syed T.,Parmeggiani, Fabio,Turner, Nicholas J.
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p. 1570 - 1576
(2017/05/05)
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- A chiral analog of the bicyclic guanidine TBD: Synthesis, structure and Br?nsted base catalysis
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Starting from (S)-β-phenylalanine, easily accessible by lipase-catalyzed kinetic resolution, a chiral triamine was assembled by a reductive amination and finally cyclized to form the title compound 10. In the crystals of the guanidinium benzoate salt the six membered rings of 10 adopt conformations close to an envelope with the phenyl substituents in pseudo-axial positions. The unprotonated guanidine 10 catalyzes Diels-Alder reactions of anthrones and maleimides (25-30% ee). It also promotes as a strong Br?nsted base the retro-aldol reaction of some cycloadducts with kinetic resolution of the enantiomers. In three cases, the retroaldol products (48-83% ee) could be recrystallized to high enantiopurity (≥95% ee). The absolute configuration of several compounds is supported by anomalous X-ray diffraction and by chemical correlation.
- Goldberg, Mariano,Sartakov, Denis,Bats, Jan W.,Bolte, Michael,G?bel, Michael W.
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supporting information
p. 1870 - 1876
(2016/10/05)
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- Influence of the aromatic moiety in α- And β-arylalanines on their biotransformation with phenylalanine 2,3-aminomutase from: Pantoea agglomerans
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In this study enantiomer selective isomerization of various racemic α- and β-arylalanines catalysed by phenylalanine 2,3-aminomutase from Pantoea agglomerans (PaPAM) was investigated. Both α- and β-arylalanines were accepted as substrates when the aryl moiety was relatively small, like phenyl, 2-, 3-, 4-fluorophenyl or thiophen-2-yl. While 2-substituted α-phenylalanines bearing bulky electron withdrawing substituents did not react, the corresponding substituted β-aryl analogues were converted rapidly. Conversion of 3- and 4-substituted α-arylalanines happened smoothly, while conversion of the corresponding β-arylalanines was poor or non-existent. In the range of pH 7-9 there was no significant influence on the conversion of racemic α- or β-(thiophen-2-yl)alanines, whereas increasing the concentration of ammonia (ammonium carbonate from 50 to 1000 mM) inhibited the isomerization progressively and decreased the amount of the by-product (i.e. (E)-3-(thiophen-2-yl)acrylic acid was detected). In all cases, the high ee values of the products indicated excellent enantiomer selectivity and stereospecificity of the isomerization except for (S)-2-nitro-α-phenylalanine (ee 92%) from the β-isomer. Substituent effects were rationalized by computational modelling revealing that one of the main factors controlling biocatalytic activity was the energy difference between the covalent regioisomeric enzyme-substrate complexes.
- Varga, Andrea,Bánóczi, Gergely,Nagy, Botond,Bencze, László Csaba,To?a, Monica Ioana,Gellért, ákos,Irimie, Florin Dan,Rétey, János,Poppe, László,Paizs, Csaba
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p. 56412 - 56420
(2016/07/06)
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- Purification and characterization of enantioselective N-acetyl-β-Phe acylases from Burkholderia sp. AJ110349
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For the production of enantiopure β-amino acids, enantioselective resolution of N-acyl β-amino acids using acylases, especially those recognizing N-acetyl- β-amino acids, is one of the most attractive methods. Burkholderia sp. AJ110349 had been reported to exhibit either (R)- or (S)-enantiomer selective Nacetyl- β-Phe amidohydrolyzing activity, and in this study, both (R)- and (S)-enantioselective N-acetyl-β- Phe acylases were purified to be electrophoretically pure and determined the sequences, respectively. They were quite different in terms of enantioselectivities and in their amino acids sequences and molecular weights. Although both the purified acylases were confirmed to catalyze N-acetyl hydrolyzing activities, neither of them show sequence similarities to the N-acetyl-α-amino acid acylases reported thus far. Both (R)- and (S)-enantioselective N-acetyl-β-Phe acylase were expressed in Escherichia coli. Using these recombinant strains, enantiomerically pure (R)-β-Phe (>99% ee) and (S)-β-Phe (>99% ee) were obtained from the racemic substrate.
- Imabayashi, Yuki,Suzuki, Shun'Ichi,Kawasaki, Hisashi,Nakamatsu, Tsuyoshi
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p. 104 - 113
(2016/03/01)
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- Haenamindole, an unusual diketopiperazine derivative from a marine-derived Penicillium sp. KCB12F005
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During the chemical investigation of marine-derived fungus, an unusual diketopiperazine (DKP) alkaloid, haenamindole (1), was isolated from a culture of the marine-derived fungus Penicillium sp. KCB12F005. The structure of 1, which possesses benzyl-hydroxypiperazindione and phenyl-pyrimidoindole rings system in the molecule, was elucidated by analysis of NMR and MS data. The stereochemistry of 1 was determined by ROESY and advanced Marfey's method.
- Kim, Jong Won,Ko, Sung-Kyun,Son, Sangkeun,Shin, Kee-Sun,Ryoo, In-Ja,Hong, Young-Soo,Oh, Hyuncheol,Hwang, Bang Yeon,Hirota, Hiroshi,Takahashi, Shunji,Kim, Bo Yeon,Osada, Hiroyuki,Jang, Jae-Hyuk,Ahn, Jong Seog
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supporting information
p. 5398 - 5401
(2015/11/09)
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- The bacterial ammonia lyase EncP: A tunable biocatalyst for the synthesis of unnatural amino acids
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Enzymes of the class I lyase-like family catalyze the asymmetric addition of ammonia to arylacrylates, yielding high value amino acids as products. Recent examples include the use of phenylalanine ammonia lyases (PALs), either alone or as a gateway to deracemization cascades (giving (S)- or (R)-α-phenylalanine derivatives, respectively), and also eukaryotic phenylalanine aminomutases (PAMs) for the synthesis of the (R)-β-products. Herein, we present the investigation of another family member, EncP from Streptomyces maritimus, thereby expanding the biocatalytic toolbox and enabling the production of the missing (S)-β-isomer. EncP was found to convert a range of arylacrylates to a mixture of (S)-α- and (S)-β-arylalanines, with regioselectivity correlating to the strength of electron-withdrawing/-donating groups on the ring of each substrate. The low regioselectivity of the wild-type enzyme was addressed via structure-based rational design to generate three variants with altered preference for either α- or β-products. By examining various biocatalyst/substrate combinations, it was demonstrated that the amination pattern of the reaction could be tuned to achieve selectivities between 99:1 and 1:99 for β:α-product ratios as desired.
- Weise, Nicholas J.,Parmeggiani, Fabio,Ahmed, Syed T.,Turner, Nicholas J.
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supporting information
p. 12977 - 12983
(2015/10/28)
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- Chemoenzymatic synthesis of both enantiomers of 3-hydroxy- and 3-amino-3-phenylpropanoic acid
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Ethyl (S)-3-hydroxy-3-phenylpropionate (S)-2 was obtained by the asymmetric reduction of ethyl 3-phenyl-3-oxopropionate 1 with the yeast Saccharomyces cerevisiae (ATCC 9080). The kinetic resolution of racemic ethyl 2-acetoxy-3-phenyl-propionate rac-3 with the same microorganism, gave after hydrolysis ethyl (R)- and (S)-3-hydroxy-3-phenylpropionates (R)-2 and (S)-2 which were converted by a straightforward series of reactions to the enantiomers of 3-amino-3-phenyl-propionic acids (S)-6 and (R)-6. The asymmetric reduction and hydrolytic kinetic resolution were also tested with several other whole cell systems under a variety of conditions.
- Varga, Annamaria,Zaharia, Valentin,Nogradi, Mihaly,Poppe, Laszlo
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p. 1389 - 1394
(2013/12/04)
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- Carica papaya lipase catalysed resolution of β-amino esters for the highly enantioselective synthesis of (S)-dapoxetine
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An efficient synthesis of the (S)-3-amino-3-phenylpropanoic acid enantiomer has been achieved by Carica papaya lipase (CPL) catalysed enantioselective alcoholysis of the corresponding racemic N-protected 2,2,2-trifluoroethyl esters in an organic solvent. A high enantioselectivity (E > 200) was achieved by two strategies that involved engineering of the substrates and optimization of the reaction conditions. Based on the resolution of a series of amino acids, it was found that the structure of the substrate has a profound effect on the CPL-catalysed resolution. The enantioselectivity and reaction rate were significantly enhanced by switching the conventional methyl ester to an activated trifluoroethyl ester. When considering steric effects, the substituted phenyl and amino groups should not both be large for the CPL-catalysed resolution. The mechanism of the CPL-catalysed enantioselective alcoholoysis of the amino acids is discussed to delineate the substrate requirements for CPL-catalysed resolution. Finally, the reaction was scaled up, and the products were separated and obtained in good yields (≥ 80 %). The (S)-3-amino-3- phenylpropanoic acid obtained was used as a key chiral intermediate in the synthesis of (S)-dapoxetine with very high enantiomeric excess (> 99 %). A carica papaya lipase catalysed resolution of N-protected β-phenylalanine esters has been developed. High enantioselectivity was achieved by two strategies that involved engineering of the substrates and optimization of the reaction conditions. After 50 % conversion, the products were separated and used as key chiral intermediates for the synthesis of (S)-dapoxetine with > 99 % ee. Copyright
- You, Pengyong,Qiu, Jian,Su, Erzheng,Wei, Dongzhi
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p. 557 - 565
(2013/03/13)
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- Enantioselective acylation of β-phenylalanine acid and its derivatives catalyzed by penicillin G acylase from alcaligenes faecalis
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This study developed a simple, efficient method for producing racemic β-phenylalanine acid (BPA) and its derivatives via the enantioselective acylation catalyzed by the penicillin G acylase from Alcaligenes faecalis (Af-PGA). When the reaction was run at 25°C and pH 10 in an aqueous medium containing phenylacetamide and BPA in a molar ratio of 2:1, 8 U/mL enzyme and 0.1 M BPA, the maximum BPA conversion efficiency at 40 min only reached 36.1%, which, however, increased to 42.9% as the pH value and the molar ratio of phenylacetamide to BPA were elevated to 11 and 3:1, respectively. Under the relatively optimum reaction conditions, the maximum conversion efficiencies of BPA derivatives all reached about 50% in a relatively short reaction time (45-90 min). The enantiomeric excess value of product (eep) and enantiomeric excess value of substrate (ees) were all above 98% and 95%, respectively. These results suggest that the method established in this study is practical, effective, and environmentally benign and may be applied to industrial production of enantiomerically pure BPA and its derivatives.
- Li, Dengchao,Ji, Lilian,Wang, Xinfeng,Wei, Dongzhi
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p. 207 - 216
(2013/04/23)
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- Asymmetric biocatalysis of S-3-amino-3-phenylpropionic acid with new isolated Methylobacterium Y1-6
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β-amino acids are widely used in drug research, and S-3-amino-3-phenylpropionic acid (S-APA) is an important pharmaceutical intermediate of S-dapoxetine, which has been approved for the treatment of premature ejaculation. Chiral catalysis is an excellent method for the preparation of enantiopure compounds. In this study, we used (±)-ethyl-3-amino-3-phenylpropanoate (EAP) as the sole carbon source. Three hundred thirty one microorganisms were isolated from 30 soil samples, and 17 strains could produce S-APA. After three rounds of cultivation and identification, the strain Y1-6 exhibiting the highest enantioselective activity of S-APA was identified as Methylobacterium oryzae. The optimal medium composition contained methanol (2.5 g/L), 1,2-propanediol (7.5 g/L), soluble starch (2.5 g/L), and peptone (10 g/L); it was shaken at 220 rpm for 4-5 days at 30 C. The optimum condition for biotransformation of EAP involved cultivation at 37 C for 48 h with 120 mg of wet cells and 0.64 mg of EAP in 1 ml of transfer solution. Under this condition, substrate ee was 92.1% and yield was 48.6%. We then attempted to use Methylobacterium Y1-6 to catalyze the hydrolytic reaction with substrates containing 3-amino-3-phenyl-propanoate ester, N-substituted-β-ethyl-3-amino-3-phenyl-propanoate, and γ-lactam. It was found that 5 compounds with ester bonds could be stereoselectively hydrolyzed to S-acid, and 2 compounds with γ-lactam bonds could be stereoselectively hydrolyzed to (-)-γ-lactam.
- Li, Yi,Wang, Wenfu,Huang, Yumian,Zou, Qianwen,Zheng, Guojun
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p. 1674 - 1678
(2013/11/19)
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- Astins K-P, six new chlorinated cyclopentapeptides from Aster tataricus
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During further investigation on the methanol extract of roots and rhizomes of Aster tataricus, six new chlorinated cyclopentapeptides, designated as astins K-P (9-14), together with eight known derivatives, astins A-H (1-8), were isolated. Structures of the new cyclopeptides were established using extensive spectroscopic methods, and the absolute configurations were determined by the advanced Marfey's method. Astin P (14) represents a unique cyclopentapeptide linking as cyclo-(l-Pro (Cl2)1-l-allo-Thr 2-l-Ser3-l-β-Phe4-l-Ava5). Astin B (2) showed cytotoxicity against BGC-823 cell with IC50 value of 19.2 μg/ml. Astin C (3) exhibited cytotoxicity on HCT-116 and BGC-823 cells with IC50 values of 13.4 and 3.3 μg/ml, respectively.
- Xu, Hui-Min,Zeng, Guang-Zhi,Zhou, Wen-Bing,He, Wen-Jun,Tan, Ning-Hua
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p. 7964 - 7969
(2013/08/23)
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- METHOD FOR OBTAINING OPTICALLY PURE AMINO ACIDS
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This invention relates to a method for obtaining optically pure amino acids, including optical resolution and optical conversion. This method significantly shortens the time taken for optical transformation, and enables the repeated use of an organic solution containing a enantioselective receptor, to thereby obtain optically pure amino acids in a simple and remarkably efficient manner, and to enable the very economical mass production of optically pure amino acids.
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Page/Page column 7
(2012/02/01)
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- Mechanism-inspired engineering of phenylalanine aminomutase for enhanced β-regioselective asymmetric amination of cinnamates
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Turn to switch: A mutant of phenylalanine aminomutase was engineered that can catalyze the regioselective amination of cinnamate derivatives (see scheme, red) to, for example, β-amino acids. This regioselectivity, along with the X-ray crystal structures, suggests two distinct carboxylate binding modes differentiated by Cβi￡Cipso bond rotation, which determines if β- (see scheme) or α-addition takes place. Copyright
- Wu, Bian,Szymanski, Wiktor,Wybenga, Gjalt G.,Heberling, Matthew M.,Bartsch, Sebastian,Dewildeman, Stefaan,Poelarends, Gerrit J.,Feringa, Ben L.,Dijkstra, Bauke W.,Janssen, Dick B.
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supporting information; experimental part
p. 482 - 486
(2012/03/22)
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- Development of a commercial process for (S)-β-phenylalanine (1)
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The development of a commercial manufacturing route for (S)-β-phenylalanine 8, a key pharmaceutical building block, is described. The different approaches which were investigated, based on catalytic asymmetric hydrogenation of enamide intermediates and on biocatalysis using acylase and lipase hydrolyses, are compared. The lipase resolution route was chosen for scale-up, and the final two-step process, based on readily available raw materials, is shown to be robust at full manufacturing scale
- Grayson, J. Ian,Roos, Juergen,Osswald, Steffen
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p. 1201 - 1206
(2011/12/16)
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- Kinetic resolution of aromatic β-amino acids by ω-transaminase
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Racemic aromatic β-amino acids have been kinetically resolved into (R)-β-amino acids with high enantiomeric excess (>99%) by a novel ω-TA with ca. 50% conversion.
- Bea, Han-Seop,Park, Hye-Jeong,Lee, Sang-Hyeup,Yun, Hyungdon
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supporting information; experimental part
p. 5894 - 5896
(2011/06/23)
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- Mechanistic, mutational, and structural evaluation of a taxus phenylalanine aminomutase
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The structure of a phenylalanine aminomutase (TcPAM) from Taxus canadensis has been determined at 2.4 A resolution. The active site of the TcPAM contains the signature 4-methylidene-1H-imidazol-5(4H)-one prosthesis, observed in all catalysts of the class I lyase-like family. This catalyst isomerizes (S)-α-phenylalanine to the (R)-β-isomer by exchange of the NH 2/H pair. The stereochemistry of the TcPAM reaction product is opposite of the (S)-β-tyrosine made by the mechanistically related tyrosine aminomutase (SgTAM) from Streptomyces globisporus. Since TcPAM and SgTAM share similar tertiary- and quaternary-structures and have several highly conserved aliphatic residues positioned analogously in their active sites for substrate recognition, the divergent product stereochemistries of these catalysts likely cannot be explained by differences in active site architecture. The active site of the TcPAM structure also is in complex with (E)-cinnamate; the latter functions as both a substrate and an intermediate. To account for the distinct (3R)-β-amino acid stereochemistry catalyzed by TcPAM, the cinnamate skeleton must rotate the C1-Cα and C ipso-β bonds 180° in the active site prior to exchange and rebinding of the NH2/H pair to the cinnamate, an event that is not required for the corresponding acrylate intermediate in the SgTAM reaction. Moreover, the aromatic ring of the intermediate makes only one direct hydrophobic interaction with Leu-104. A L104A mutant of TcPAM demonstrated an ～1.5-fold increase in kcat and a decrease in KM values for sterically demanding 3′-methyl-α-phenylalanine and styryl-α-alanine substrates, compared to the kinetic parameters for TcPAM. These parameters did not change significantly for the mutant with 4′-methyl-α-phenylalanine compared to those for TcPAM.(Figure Presented)
- Feng, Lei,Wanninayake, Udayanga,Strom, Susan,Geiger, James,Walker, Kevin D.
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experimental part
p. 2919 - 2930
(2012/07/14)
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- Stereochemistry and mechanism of a microbial phenylalanine aminomutase
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The stereochemistry of a phenylalanine aminomutase (PAM) on the andrimid biosynthetic pathway in Pantoea agglomerans (Pa) is reported. PaPAM is a member of the 4-methylidene-1H-imidazol-5(4H)-one (MIO)-dependent family of catalysts and isomerizes (2S)-α-phenylalanine to (3S)-β-phenylalanine, which is the enantiomer of the product made by the mechanistically similar aminomutase TcPAM from Taxus plants. The NH2 and pro-(3S) hydrogen groups at Cα and Cβ, respectively, of the substrate are removed and interchanged completely intramolecularly with inversion of configuration at the migration centers to form β-phenylalanine. This is a contrast to the retention of configuration mechanism followed by TcPAM.
- Ratnayake, Nishanka Dilini,Wanninayake, Udayanga,Geiger, James H.,Walker, Kevin D.
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supporting information; experimental part
p. 8531 - 8533
(2011/07/29)
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- Stereoselective chemoenzymatic preparation of β-amino esters: Molecular modelling considerations in lipase-mediated processes and application to the synthesis of (S)-dapoxetine
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A wide range of optically active 3-amino-3-arylpropanoic acid derivatives have been prepared by means of a stereoselective chemoenzymatic route. The key step is the kinetic resolution of the corresponding β-amino esters. Although the enzymatic acylations of the amino group with ethyl methoxyacetate showed synthetically useful enantioselectivities, the hydrolyses of the ester group catalyzed by lipase from Pseudomonas cepacia have been identified as the optimal processes concerning both activity and enantioselectivity. The enantiopreference of this lipase in these reactions has been explained, at the molecular level, by using a fragment-based approach in which the most favoured binding site for a phenyl ring and the most stable conformation of the 3-aminopropanoate core nicely match the (S)-configuration of the major products. The conversion and enantioselectivity values of the enzymatic reactions have been compared in order to understand the influence of the different substitution patterns present in the phenyl ring. This chemoenzymatic route has been successfully applied to the preparation of a valuable intermediate in the synthesis of (S)-dapoxetine, which has been chemically synthesised in excellent optical purity.
- Rodriguez-Mata, Maria,Garcia-Urdiales, Eduardo,Gotor-Fernandez, Vicente,Gotor, Vicente
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supporting information; experimental part
p. 395 - 406
(2010/06/15)
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- Doubly diastereoselective conjugate addition of enantiopure lithium amides to enantiopure N-enoyl oxazolidin-2-ones: A mechanistic probe
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The doubly diastereoselective conjugate addition of the antipodes of lithium N-benzyl-N-(α-methylbenzyl)amide to a range of enantiopure N-enoyl oxazolidin-2-ones has been used as a mechanistic probe to determine that the reactive conformation is the anti-s-cis form. The β-amino carbonyl products resulting from these conjugate addition reactions are useful templates for further elaboration into an α,β,α-pseudotripeptide.
- Davies, Stephen G.,Fletcher, Ai M.,Hermann, Gesine J.,Poce, Giovanna,Roberts, Paul M.,Smith, Andrew D.,Sweet, Miles J.,Thomson, James E.
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experimental part
p. 1635 - 1648
(2010/10/18)
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- Magnesium(II)-binaphtholate as a practical chiral catalyst for the enantioselective direct mannich-type reaction with malonates
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(Equation Presented). A highly enantioselective direct Mannich-type reaction of aldimines with dialkyl malonates was developed with the use of a Mg(II)-BINOLate salt, which was designed as a cooperative acid-base catalyst that can activate both aldimines and malonates. Optically active β-aminoesters and α-halo-β-aminoesters could be synthesized in high yields and with high enantioselectivities. This inexpensive and practical Mg(II)-BINOLate salt could be used in gram-scale catalysis.
- Hatano, Manabu,Horibe, Takahiro,Ishihara, Kazuaki
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supporting information; experimental part
p. 3502 - 3505
(2010/09/11)
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- Rhodium-catalyzed asymmetric addition of arylboronic acids to β-phthaliminoacrylate esters toward the synthesis of β-amino acids
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(Chemical Equation Presented) Rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to β-phthaliminoacrylate esters took place efficiently to give high yields of β-aryl-β-amino acid esters with 96-99% enantioselectivity, which was realized by use of a hydroxorhodium/chiral diene complex. Copyright
- Nishimura, Takahiro,Wang, Jun,Nagaosa, Makoto,Okamoto, Kazuhiro,Shintani, Ryo,Kwong, Fuk-Yee,Yu, Wing-Yiu,Chan, Albert S. C.,Hayashi, Tamio
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supporting information; experimental part
p. 464 - 465
(2010/03/25)
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- Enantiomerically pure β-phenylalanine analogues from α-β-phenylalanine mixtures in a single reactive extraction step
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An efficient and selective method for the extraction of α-amino acids in preference over their β-isomers using PdCl2(PPh 3)2 was discovered, which enables the separation of product mixtures obtained in the enantioselective enzymatic formation of β-amino acids. The Royal Society of Chemistry 2010.
- Verkuijl, Bastiaan J. V.,Szymanski, Wiktor,Wu, Bian,Minnaard, Adriaan J.,Janssen, Dick B.,De Vries, Johannes G.,Feringa, Ben L.
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scheme or table
p. 901 - 903
(2010/06/12)
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- Diastereoselective Michael addition of magnesium amide to O-(2-Alkenoyl)TEMPOs and comparison of reactivity with acyl substituent-modified carboxylic analogues
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O-(2-Alkenoyl)TEMPOs bearing an ON bond in the acyl substituent are highly reactive in Michael addition of magnesium amide compared with their acyl substituent-modified analogs. Highly diastereoselective addition is achieved to the AlMe3-treated O-(2-alkenoyl)TEMPO as an acceptor with the Mg amide generated from optically active secondary amine.
- Ma, Li-Jian,Mei, Zhen-Wu,Toyohara, Keisuke,Kawafuchi, Hiroyuki,Nokami, Junzo,Inokuchi, Tsutomu
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p. 1545 - 1547
(2011/03/16)
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- Efficient tandem biocatalytic process for the kinetic resolution of aromatic β-amino acids
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We describe a simple and efficient enzymatic tandem reaction for the preparation of enantiomerically pure β-phenylalanine and its analogues from the corresponding racemates. In this process, phenylalanine aminomutase (PAM) catalyzes the stereoselective isomerization of (R)-β-phenylalanines to (S)-a-phenylalanines, which are in situ transformed to cinnamic acids by phenylalanine ammonia lyase (PAL). Preparative scale conversions are done with a mutated PAM with enhanced catalytic activity.
- Wu, Bian,Szymanski, Wiktor,De Wildeman, Stefaan,Poelarends, Gerrit J.,Feringa, Ben L.,Janssen, Dick B.
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supporting information; experimental part
p. 1409 - 1412
(2010/08/19)
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- COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS
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The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.
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Page/Page column 45-49; 60
(2010/12/31)
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- Enhanced conversion of racemic α-arylalanines to (R)-β- arylalanines by coupled racemase/aminomutase catalysis
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(Graph Presented) The Taxus phenylalanine aminomutase (PAM) enzyme converts several (S)-α-arylalanines to their corresponding (R)-β- arylalanines. After incubating various racemic substrateswith 100 μg of PAM for 20 h at 31°C, each (S)-α-arylalanine was enantioselectively isomerized to its corresponding (R)-β-product. With racemic starting materials, the ratio of (R)-β-arylalanine product to the (S)-α-substrate ranged between 0.4 and 1.8, and the remaining nonproductive (R)-α-arylalanine became enriched. To utilize the (R)-α-isomer, the catalysis of a promiscuous alanine racemase from Pseudomonas putida (KT2440) was coupled with that of PAM to increase the production of enantiopure (R)-β-arylalanines from racemic α-arylalanine substrates. The inclusion of a biocatalytic racemization along with the PAM-catalyzed reactionmoderately increased the overall reaction yield of enantiopure β-arylalanines between 4% and 19% (depending on the arylalanine), which corresponded to as much as a 63% increase compared to the turnover with the aminomutase reaction alone. The use of these biocatalysts, in tandem, could potentially find application in the production of chiral β-arylalanine building blocks, particularly, as refinements to the process are made that increase reaction flux, such as by selectively removing the desired (R)-β-arylalanine product from the reaction mixture. 2009 American Chemical Society.
- Cox, Brad M.,Bilsborrow, Joshua B.,Walker, Kevin D.
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experimental part
p. 6953 - 6959
(2009/12/25)
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- Phenylalanine aminomutase-catalyzed addition of ammonia to substituted cinnamic acids: A route to enantiopure α- and β-amino acids
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(Chemical Equation Presented) An approach is described for the synthesis of aromatic α- and β-amino acids that uses phenylalanine aminomutase to catalyze a highly enantioselective addition of ammonia to substituted cinnamic acids. The reaction has a broad scope and yields substituted α- and β-phenylalanines with excellent enantiomeric excess. The regioselectivity of the conversion is determined by substituents present at the aromatic ring. A box model for the enzyme active site is proposed, derived from the influence of the hydrophobicity of substituents on the enzyme affinity toward various substrates.
- Szymanski, Wiktor,Wu, Bian,Weiner, Barbara,De Wildeman, Stefaan,Feringa, Ben L.,Janssen, Dick B.
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supporting information; experimental part
p. 9152 - 9157
(2010/03/01)
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- Synthetic and pharmacological studies on new simplified analogues of the potent actin-targeting Jaspamide
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In the recent years, we focused our attention on the cyclodepsipeptide Jaspamide 1, an interesting marine metabolite, possessing a potent inhibitory activity against breast and prostate cancer, as a consequence of its ability to disrupt actin cytoskeleton dynamics. Although its biological profile has been well determined, many mechanistic details are still missing in terms of molecular target identification. For this reason, we decided to synthetically modify the natural metabolite, obtaining small arrays of unnatural variants useful to illuminate the structural requirements essential for the activity. Here, we report the synthesis of seven new Jaspamide analogues 2-8, containing, as the parent compound, a β-amino acid in the cyclopeptide backbone. Their biological profile is also described.
- Terracciano, Stefania,Bruno, Ines,D'Amico, Elisabetta,Bifulco, Giuseppe,Zampella, Angela,Sepe, Valentina,Smith, Charles D.,Riccio, Raffaele
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p. 6580 - 6588
(2008/12/21)
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- An efficient new enzymatic method for the preparation of β-aryl-β-amino acid enantiomers
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An efficient synthesis of β-aryl-β-amino acid enantiomers has been developed via the lipase-catalysed enantioselective hydrolysis of the corresponding racemic ethyl esters in an organic solvent. High enantioselectivities (E >100) were observed when the lipase PS-catalysed reactions were performed with H2O (0.5 equiv) in diisopropyl ether at 45 °C. The products could be easily separated and were obtained in good yields of ≥40%.
- Tasnadi, Gabor,Forro, Eniko,Fueloep, Ferenc
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p. 2072 - 2077
(2008/12/22)
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- Catalytic enantioselective 5-hydroxyisoxazolidine synthesis: An asymmetric entry to β-amino acids
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The highly chemo- and enantioselective organocatalytic tandem reaction between N-carbamate-protected hydroxylamines and α,β-unsaturated aldehydes is presented. The reaction represents a unique entry for the asymmetric synthesis of 5-hydroxyisoxazolidines, oxazolidin-5-ones or γ-hydroxyamino alcohols in high yields and 90-99% ee. A procedure for the conversion of the oxazolidin-5-ones into the corresponding β-amino acids is also described. Georg Thieme Verlag Stuttgart.
- Ibrahem, Ismail,Rios, Ramon,Vesely, Jan,Zhao, Gui-Ling,Cordova, Armando
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p. 1153 - 1157
(2008/12/22)
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- Solid phase synthesis of novel α/β-tetrapeptides, electrospray ionization mass spectrometric evaluation of their metal cation complexation behavior, and conformational analysis using density functional theory (DFT)
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Thirty-four novel α/β-tetrapeptides (1-34) have been prepared employing solid-phase and in-parallel synthetic protocols. α/β- Tetrapeptides 1-34 were prepared by a combination of three α-amino acid residues (alanine (Ala), phenylalanine (Phe), and isoleucine (Ile)) with one β-amino acid residue (β3-homophenylglycine). The corresponding complexes of several selected α/β-tetrapeptides with alkali, alkaline earth, and transition metals, [tP + M+], were evaluated using ion electrospray-ionization mass spectrometry (ESI-MS). According to the results from analysis of mixtures, we can conclude that the position of the β-amino acid is determinant in the affinity toward different metal cations. Computational modeling (DFT, B3LYP 6-311++G) provided useful information regarding the most likely coordination sites of the metal ions on the receptor α/β-tetrapeptide 12, HO2C-α- Phe-α-Phe-α-Ile-β3-hPhg-NH2, as well as the conformational changes induced by the metal upon [tP + M+] complex formation. Copyright
- Bandala, Yamir,Avina, Judit,Gonzalez, Tania,Rivero, Ignacio A.,Juaristi, Eusebio
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p. 349 - 358
(2008/12/20)
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- Enantioselective acylation of alcohols with fluorinated β-phenyl-β-lactams in the presence of Burkholderia cepacia lipase
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This paper concentrates on studies of the acylation of alcohols with 3,3-difluoro-4-phenylazetidin-2-one rac-1, trans-3-fluoro-4-phenylazetidin-2-one rac-2 and 4-phenylazetidin-2-one rac-3 in the presence of immobilized lipase PS from Burkholderia cepacia in dry tert-butyl methyl ether (TBME). Fluorine activation in the compounds studied was essential in order to split the β-lactam ring with lipase PS. The highly enantioselective ring opening of rac-1 and rac-2 with methanol (1-butanol was also studied) allowed the preparation of the (R/(3R,4R))-β-lactams as the unreacted enantiomers and (S/(2S,3S))-β-amino esters as the product enantiomers with an ee >99%. Under the same conditions, rac-3 was totally unreactive. The possibility for a competing hydrolysis caused by water in the enzyme preparations is also discussed.
- Li, Xiang-Guo,Laehitie, Maria,Paeivioe, Mari,Kanerva, Liisa T.
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p. 1567 - 1573
(2008/02/11)
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- Parallel synthesis of homochiral β-amino acids
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The parallel asymmetric synthesis of an array of 30 β-amino acids of high enantiomeric purity using the conjugate addition of homochiral lithium N-benzyl-N-(α-methylbenzyl)amide as the key step is accomplished. The experimental simplicity and highly practical nature of the protocol is demonstrated by the efficient parallel conversion of 15 α,β-unsaturated esters to both enantiomeric series of the corresponding β-amino acids in high overall yields and selectivities with minimal purification involved in each step of the reaction protocol.
- Davies, Stephen G.,Mulvaney, Andrew W.,Russell, Angela J.,Smith, Andrew D.
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p. 1554 - 1566
(2008/02/09)
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- Organocatalytic asymmetric 5-hydroxyisoxazolidine synthesis: A highly enantioselective route to β-amino acids
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The highly chemo- and enantioselective organocatalytic tandem reaction between N-protected hydroxyl amines and α,β-unsaturated aldehydes is presented; the reaction provides access to 5-hydroxyisoxazolidines and β-amino acids in high yields and with 90-99% ee. The Royal Society of Chemistry.
- Ibrahem, Ismail,Rios, Ramon,Vesely, Jan,Zhao, Gui-Ling,Cordova, Armando
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p. 849 - 851
(2007/10/03)
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- β-styryl- and β-aryl-β-alanine products of phenylalanine aminomutase catalysis
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The substrate specificity of a Taxus-derived phenylalanine aminomutase (PAM) was investigated, and the enzyme was found to catalyze the conversion of variously substituted vinyl- and aryl-S-∞-alanines to corresponding β-amino acids. This study shows the b
- Klettke, Karin L.,Sanyal, Sanjit,Mutatu, Washington,Walker, Kevin D.
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p. 6988 - 6989
(2008/02/06)
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- 3-AMINO-3-ARYLPROPIONIC ACID n-ALKYL ESTERS, PROCESS FOR PRODUCTION THEREOF, AND PROCESS FOR PRODUCTION OF OPTICALLY ACTIVE 3-AMINO-3-ARYLPROPIONIC ACIDS AND ESTERS OF THE ANTIPODES THERETO
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The present invention is to provide an n-alkyl 3-amino-3-arylpropionate represented by the formula (I): wherein Ar1 represents an aryl group which may have a substituent(s), provided that a phenyl group and 4-methoxyphenyl group are excluded, R1 represents an n-propyl group or an n-butyl group, and a process for preparing the same, and its optically active compound and an optically active (S or R)-3-amino-3-arylpropionic acid represented by the formula (III-a): wherein Ar represents an aryl group which may have a substituent(s), and * represents an asymmetric carbon, and a process for preparing an optically active n-alkyl (R or S)-3-amino-3-arylpropionate represented by the formula (IV-a): wherein Ar and R1 have the same meanings as defined above, * represents an asymmetric carbon, provided that it has a reverse absolute configuration to the compound of the formula (III-a).
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Page/Page column 25-26
(2008/06/13)
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- Homochiral lithium amides for the asymmetric synthesis of β-amino acids
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Secondary homochiral lithium amides derived from α-methylbenzylamine undergo highly diastereoselective conjugate additions to a range of α,β-unsaturated esters. The corresponding β-amino acids are readily liberated by successive N-debenzylation and ester hydrolysis, furnishing (R)-β-amino butyric acid, (R)-β-amino pentanoic acid, (S)-β-leucine, (R)-β-amino octanoic acid, (S)-β-phenylalanine, (S)-β-tyrosine methyl ether, (S)-β-tyrosine hydrochloride and (S)-β-(2-methoxyphenyl)-β-amino propanoic acid in high yields and high ee. The application of this procedure to the synthesis of the natural products (R)-β-DOPA and (R)-β-lysine is demonstrated. The development of a simplified one-pot reaction protocol applicable to the multi-gram scale synthesis of homochiral β-amino esters is also delineated.
- Davies, Stephen G.,Garrido, Narciso M.,Kruchinin, Dennis,Ichihara, Osamu,Kotchie, Luke J.,Price, Paul D.,Mortimer, Anne J. Price,Russell, Angela J.,Smith, Andrew D.
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p. 1793 - 1811
(2007/10/03)
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- Microbial production of optically active β-phenylalanine through stereoselective degradation of racemic β-phenylalanine
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The ability to produce (R)- or (S)-β-phenylalanine from racemic β-phenylalanine through stereoselective degradation was screened for. Variovorax sp. JH2 and Arthrobacter sp. the faculty of Agriculture, Kyoto University (AKU) 638 were found to be potential catalysts for (R)- and (S)-β-phenylalanine production respectively. On 192 h cultivation of Variovorax sp. in medium containing 1.0% (w/v) racemic β-phenylalanine, 0.46% (w/v) (R)-β-phenylalanine with an enantiomeric purity of 99% e.e. was obtained. The initial step of the (S)-isomer degradation was stereoselective transamination. On 312 h cultivation of Arthrobacter sp. in medium containing 1.0% (w/v) racemic β-phenylalanine, 0.51% (w/v) (R)-β-phenylalanine with an enantiomeric purity of 90% e.e. was obtained. The initial step of the (R)-isomer degradation was supposed to be oxidative deamination. Resting cell reaction with vigorous shaking, with cells of Arthrobacter sp. as the catalyst, resulted in production of 0.49% (w/v) of (S)-β-phenylalanine with an enantiomeric purity of 99% e.e. from 1.0% (w/v) racemic β-phenylalanine in 45 h.
- Mano, Junichi,Ogawa, Jun,Shimizu, Sakayu
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p. 1941 - 1946
(2008/02/13)
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- Production of (R)-3-amino-3-phenylpropionic acid and (S)-3-amino-3- phenylpropionic acid from (R,S)-N-acetyl-3-amino-3-phenylpropionic acid using microorganisms having enantiomer-specific amidohydrolyzing activity
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(R)-3-Amino-3-phenylpropionic acid ((R)-β-Phe) and (S)-3-amino-3-phenylpropionic acid ((S)-β-Phe) are key compounds on account of their use as intermediates in synthesizing pharmaceuticals. Enantiomerically pure non-natural amino acids are generally prepared by enzymatic resolution of the racemic N-acetyl form, but despite the intense efforts this method could not be used for preparing enantiomerically pure β-Phe, because the effective enzyme had not been found. Therefore, screening for microorganisms capable of amidohydrolyzing (R,S)-N-acetyl-3-amino-3-phenylpropionic acid ((R,S)-N-Ac-β-Phe) in an enantiomer-specific manner was performed. A microorganism having (R)-enantiomer-specific amidohydrolyzing activity and another having both (R)-enantiomer- and (S)-enantiomer-specific amidohydrolyzing activities were obtained from soil samples. Using 16S rDNA analysis, the former organism was identified as Variovorax sp., and the latter as Burkholderia sp. Using these organisms, enantiomerically pure (R)-β-Phe (> 99.5% ee) and (S)-β-Phe (> 99.5% ee) with a high molar conversion yield (67%-96%) were obtained from the racemic substrate.
- Kawasaki, Hisashi,Koyama, Koutaro,Kurokawa, Sachio,Watanabe, Kunihiko,Nakazawa, Masakazu,Izawa, Kunisuke,Nakamatsu, Tsuyoshi
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- Enantioselective enzymatic reactions in miniemulsions as efficient "nanoreactors"
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(Chemical Equation Presented) Phasing in: Miniemulsions are homogenous mixtures in which the organic phase is dispersed in the form of nanometer-scale droplets, which can act as efficient "nanoreactors" for enantioselective enzymatic transformations. Very high substrate concentrations are possible, and both α- and β-amino acids were prepared with high conversions and up to > 99% ee.
- Groeger, Harald,May, Oliver,Huesken, Hendrik,Georgeon, Sandrine,Drauz, Karlheinz,Landfester, Katharina
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p. 1645 - 1648
(2008/02/02)
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- A new route to enantiopure β-aryl-substituted β-amino acids and 4-aryl-substituted β-lactams through lipase-catalyzed enantioselective ring cleavage of β-lactams
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A simple and efficient direct enzymatic method was developed for the synthesis of 4-aryl-substituted β-lactams and the corresponding β-amino acid enantiomers through the CAL-B (lipase B from Candida antarctica)-catalyzed enantioselective (E > 200) ring cleavage of the corresponding racemic β-lactams with 1 equiv. of H2O in i-Pr2O at 60°C. The product (R)-β-amino acids (ee ≥ 98%, yields ≥ 42%) and unreacted (S)-β-lactams (ee ≥ 95%, yields ≥ 41%) could be easily separated. The ring opening of enantiomeric β-lactams with 18% HCl afforded the corresponding enantiopure β-amino acid hydrochlorides (ee ≥ 99%).
- Forro, Eniko,Paal, Tihamer,Tasnadi, Gabor,Fueloep, Ferenc
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p. 917 - 923
(2007/10/03)
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- Enzymatic process for the enantiomeric resolution of amino acids
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An enzymatic process permitting the enantiomeric resolution of amino acids is provided. More specifically, this process for separating the enantiomers of an amino acid comprises treating a racemic mixture of the amino acid with glutaric anhydride and then with the enzyme glutaryl-7-ACA acylase so as to recover one of the enantiomers of the amino acid, the other enantiomer remaining in the form of the corresponding glutarylamide derivative.
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