4286-15-1Relevant articles and documents
Enantioselective α-alkylation of phenylacetic acid using a chiral bidentate lithium amide as a chiral auxiliary
Matsuo, Jun-Ichi,Koga, Kenji
, p. 2122 - 2124 (1997)
Enantioselective alkylation at the α-position of phenylacetic acid (1) can be realized in up to 68% ee by treating the dilithiated 1 with alkyl halides in the presence of a chiral bidentate lithium amicle ((R)-3).
Deracemizing α-Branched Carboxylic Acids by Catalytic Asymmetric Protonation of Bis-Silyl Ketene Acetals with Water or Methanol
Mandrelli, Francesca,Blond, Aurélie,James, Thomas,Kim, Hyejin,List, Benjamin
supporting information, p. 11479 - 11482 (2019/07/18)
We report a highly enantioselective catalytic protonation of bis-silyl ketene acetals. Our method delivers α-branched carboxylic acids, including nonsteroidal anti-inflammatory arylpropionic acids such as Ibuprofen, in high enantiomeric purity and high yields. The process can be incorporated in an overall deracemization of α-branched carboxylic acids, involving a double deprotonation and silylation followed by the catalytic asymmetric protonation.
Modeling and optimization of lipase-catalyzed hydrolysis for production of (S)-2-phenylbutyric acid enhanced by hydroxyethyl-β-cyclodextrin
Zhang, Panliang,Cheng, Qing,Xu, Weifeng,Tang, Kewen
, p. 96 - 103 (2019/05/27)
An efficient reactive system was established to produce (S)-2-phenylbutyric acid (2-PBA) through the enzymatic enantioselective hydrolysis of 2-phenylbutyrate ester (2-PBAE) in aqueous medium. Lipase CALA from Canadian antarctica and hexyl 2-phenylbutyrate (2-PBAHE) were identified upon screening as the best enzyme and substrate, respectively. Adding hydroxyethyl-β-cyclodextrin (HE-β-CD) to improve the solubility of the substrate resulted in a 1.5 times increase in substrate conversion while retaining a high enantioselectivity compared with that when HE-β-CD was not added. The effects of lipase concentration, substrate concentration and HE-β-CD concentration, temperature, pH, and reaction time on enantiomeric excess and conversion rate were investigated, and the optimal conditions were identified using response surface methodology (RSM). Under the optimal conditions, namely 50 mg/mL lipase CALA, 30 mmol/L substrate, 60 mmol/L HE-β-CD, pH of 6.5, temperature of 83 °C and reaction time of 18 h, the enantiomeric excess and overall conversion rate were 96.05% and 27.28%, respectively. This work provides an efficient alternative method for improving the conversion of aromatic ester substrates by including β-cyclodextrin in an aqueous hydrolysis reaction system.
Entrapment of a chiral cobalt complex within silver: A novel heterogeneous catalyst for asymmetric carboxylation of benzyl bromides with CO2
Yang, Heng-Pan,Yue, Ying-Na,Sun, Qi-Long,Feng, Qiu,Wang, Huan,Lu, Jia-Xing
supporting information, p. 12216 - 12219 (2015/07/27)
A novel way to accommodate heterogeneous catalysis, CO2 fixation and asymmetric synthesis on one catalyst is reported. The [Co]@Ag composite was prepared for the first time and used for asymmetric carboxylation of benzyl bromides with CO2. All the procedures were performed under mild conditions. Moreover, the [Co]@Ag composite has terrific stability and reusability.
Substrate evaluation of rhodococcus erythropolis SET1, a nitrile hydrolysing bacterium, demonstrating dual activity strongly dependent on nitrile sub-structure
Coady, Tracey M.,Coffey, Lee V.,O'Reilly, Catherine,Lennon, Claire M.
supporting information, p. 1108 - 1116 (2015/02/19)
Assessment of Rhodococcus erythropolis SET1, a novel nitrile hydrolysing bacterial isolate, has been undertaken with 34 nitriles, 33 chiral and 1 prochiral. These substrates consist primarily of β-hydroxy nitriles with varying alkyl and aryl groups at the β position and containing in several compounds different substituents α to the nitrile. In the case of β-hydroxy nitriles without substitution at the α position, acids were the major products obtained, along with recovered nitrile after biotransformation, as a result of suspected nitrilase activity of the isolate. Unexpectedly, amides were found to be the major hydrolysis product when the β-hydroxy nitriles possessed a vinyl group at this position. To probe this behaviour further, additional related substrates were evaluated containing electron-withdrawing groups at the α position, and amide was also observed upon biotransformation in the presence of SET1. Therefore this novel isolate has also demonstrated NHase activity with nitriles that appears to be substrate-dependent.
Effect of the concentration of organic modifier in an aqueous-ethanol mobile phase on the chromatographic retention and thermodynamic characteristics of the adsorption of enantiomers of α-phenylcarboxylic acids on silica gel with immobilized eremomycin antibiotic
Blinov,Reshetova
, p. 1778 - 1784 (2014/11/08)
Regularities of the chromatographic retention and thermodynamics of the adsorption of enantiomers of α-phenylcarboxylic acids on a chiral stationary phase with immobilized macrocyclic antibiotic eremomycin under conditions of reversed-phase liquid chromatography with aqueous-ethanol mobile phases are studied. Relationships between the retention characteristics of the acids, the enantioselectivity of their separation, and the concentration of organic modifier in the mobile phase are found. It is shown that the sterical structure of substituents on the chiral atoms of the acids affect the mechanism of retention. The compensation effect in the studied systems is considered.
Laboratory evolution of enantiocomplementary Candida antarctica lipase B mutants with broad substrate scope
Wu, Qi,Soni, Pankaj,Reetz, Manfred T.
, p. 1872 - 1881 (2013/08/24)
Candida antarctica lipase B (CALB) is a robust and easily expressed enzyme used widely in academic and industrial laboratories with many different kinds of applications. In fine chemicals production, examples include acylating kinetic resolution of racemic secondary alcohols and amines as well as desymmetrization of prochiral diols (or the reverse hydrolytic reactions). However, in the case of hydrolytic kinetic resolution of esters or esterifying kinetic resolution of acids in which chirality resides in the carboxylic acid part of the substrate, rate and stereoselectivity are generally poor. In the present study, directed evolution based on iterative saturation mutagenesis was applied to solve the latter problem. Mutants with highly improved activity and enantioselectivity relative to wild-type CALB were evolved for the hydrolytic kinetic resolution of p-nitrophenyl 2-phenylpropanoate, with the selectivity factor increasing from E = 1.2 (S) to E = 72 (S) or reverting to E = 42 (R) on an optional basis. Surprisingly, point mutations both in the acyl and alcohol pockets of CALB proved to be necessary. Some of the evolved CALB mutants are also efficient biocatalysts in the kinetic resolution of other chiral esters without performing new mutagenesis experiments. Another noteworthy result concerns the finding that enantiocomplementary CALB mutants for α-substituted carboxylic acid esters also show stereocomplementarity in the hydrolytic kinetic resolution of esters derived from chiral secondary alcohols. Insight into the source of stereoselectivity was gained by molecular dynamics simulations and docking experiments.
Palladium-catalyzed allylic cross-coupling reactions of primary and secondary homoallylic electrophiles
Stokes, Benjamin J.,Opra, Susanne M.,Sigman, Matthew S.
supporting information; experimental part, p. 11408 - 11411 (2012/09/05)
The Pd(0)-catalyzed allylic cross-coupling of homoallylic tosylate substrates using boronic acids and pinacol esters is reported. The reaction uses 2-(4,5-dihydro-2-oxazolyl)quinoline (quinox) as a ligand and is performed at ambient temperature. The scope of the reaction is broad in terms of both the boronate transmetalating reagent and the substrate and includes secondary tosylates. Mechanistic studies support an alkene-mediated SN2-type stereoinvertive oxidative addition of unactivated primary and secondary alkyl tosylates.
Highly enantioselective direct alkylation of arylacetic acids with chiral lithium amides as traceless auxiliaries
Stivala, Craig E.,Zakarian, Armen
supporting information; experimental part, p. 11936 - 11939 (2011/09/19)
A direct, highly enantioselective alkylation of arylacetic acids via enediolates using a readily available chiral lithium amide as a stereodirecting reagent has been developed. This approach circumvents the traditional attachment and removal of chiral auxiliaries used currently for this type of transformation. The protocol is operationally simple, and the chiral reagent is readily recoverable.
Efficient parallel resolution of pentafluorophenyl active esters using quasi-enantiomeric combinations of oxazolidin-2-ones
Shaye, Najla Al,Chavda, Sameer,Coulbeck, Elliot,Eames, Jason,Yohannes, Yonas
experimental part, p. 439 - 463 (2011/06/17)
The parallel resolution of racemic pentafluorophenyl 2-aryl/ phenylpropanoates and butanoates using an equimolar combination of quasi-enantiomeric Evans oxazolidin-2-ones is discussed. The levels of diastereoselectivity were excellent (>90% de) leading to separable quasi-enantiomeric oxazolidin-2-ones in good yield. This methodology was used to resolve a series of structurally related 2-aryl/phenylpropanoic and butanoic acids.
