- Enantioselective α-alkylation of phenylacetic acid using a chiral bidentate lithium amide as a chiral auxiliary
-
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).
- Matsuo, Jun-Ichi,Koga, Kenji
-
-
Read Online
- Modeling and optimization of lipase-catalyzed hydrolysis for production of (S)-2-phenylbutyric acid enhanced by hydroxyethyl-β-cyclodextrin
-
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.
- Zhang, Panliang,Cheng, Qing,Xu, Weifeng,Tang, Kewen
-
-
- Deracemizing α-Branched Carboxylic Acids by Catalytic Asymmetric Protonation of Bis-Silyl Ketene Acetals with Water or Methanol
-
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.
- Mandrelli, Francesca,Blond, Aurélie,James, Thomas,Kim, Hyejin,List, Benjamin
-
p. 11479 - 11482
(2019/07/18)
-
- Entrapment of a chiral cobalt complex within silver: A novel heterogeneous catalyst for asymmetric carboxylation of benzyl bromides with CO2
-
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.
- Yang, Heng-Pan,Yue, Ying-Na,Sun, Qi-Long,Feng, Qiu,Wang, Huan,Lu, Jia-Xing
-
supporting information
p. 12216 - 12219
(2015/07/27)
-
- Substrate evaluation of rhodococcus erythropolis SET1, a nitrile hydrolysing bacterium, demonstrating dual activity strongly dependent on nitrile sub-structure
-
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.
- Coady, Tracey M.,Coffey, Lee V.,O'Reilly, Catherine,Lennon, Claire M.
-
supporting information
p. 1108 - 1116
(2015/02/19)
-
- 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
-
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.
- Blinov,Reshetova
-
p. 1778 - 1784
(2014/11/08)
-
- Laboratory evolution of enantiocomplementary Candida antarctica lipase B mutants with broad substrate scope
-
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.
- Wu, Qi,Soni, Pankaj,Reetz, Manfred T.
-
p. 1872 - 1881
(2013/08/24)
-
- Palladium-catalyzed allylic cross-coupling reactions of primary and secondary homoallylic electrophiles
-
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.
- Stokes, Benjamin J.,Opra, Susanne M.,Sigman, Matthew S.
-
supporting information; experimental part
p. 11408 - 11411
(2012/09/05)
-
- Efficient parallel resolution of pentafluorophenyl active esters using quasi-enantiomeric combinations of oxazolidin-2-ones
-
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.
- Shaye, Najla Al,Chavda, Sameer,Coulbeck, Elliot,Eames, Jason,Yohannes, Yonas
-
experimental part
p. 439 - 463
(2011/06/17)
-
- Highly enantioselective direct alkylation of arylacetic acids with chiral lithium amides as traceless auxiliaries
-
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.
- Stivala, Craig E.,Zakarian, Armen
-
supporting information; experimental part
p. 11936 - 11939
(2011/09/19)
-
- Resolution of pentafluorophenyl esters using oxazolidin-2-ones
-
A series of structurally related racemic pentafluorophenyl active esters were resolved using an equimolar amount of (S)-4-phenyloxazolidin-2-one. The levels of diastereocontrol were found to be excellent (80-96% de) at ~40% conversion.
- Al Shaye, Najla,Eames, Jason
-
scheme or table
p. 5892 - 5895
(2010/11/18)
-
- High-performance liquid chromatography separation of enantiomers of mandelic acid and its analogs on a chiral stationary phase
-
The enantiomers of mandelic acid and its analogs have been chromatographically separated on a chiral stationary phase (CSP) derived from 4-(3,5-dinitrobenzamido) tetrahydrophenanthrene. The rationale of separations of these compounds is discussed with respect to the method development for determining enantiomeric purity and possibility of obtaining enantiomerically pure materials by high-pressure liquid chromatography. The relationship of analyte structure to the extent of enantiomeric separation has been examined and separation factors (a) are presented for various groups of structurally related compounds. Chiral recognition models have been suggested to account for the observed separations. These models provide mechanistic insights into the chiral recognition process.
- Aneja, Ritu,Luthra, Pratibha Mehta,Ahuja, Satinder
-
experimental part
p. 479 - 485
(2010/08/20)
-
- METHOD FOR PRODUCING OPTICALLY ACTIVE ESTER AND METHOD FOR PRODUCING OPTICALLY ACTIVE CARBOXYLIC ACID
-
Disclosed is a method for producing an optically active ester by highly selectively esterifying one enantiomer of a racemic carboxylic acid, while producing an optically active carboxylic acid which is the other enantiomer. An optically active ester is produced while producing an optically active carboxylic acid at the same time by reacting a racemic carboxylic acid with a specific alcohol or phenol derivative in the presence of benzoic anhydride or a derivative thereof and a catalyst such as tetramisole or benzotetramisole, thereby selectively esterifying one enantiomer of the racemic carboxylic acid.
- -
-
Page/Page column 8-10
(2010/09/18)
-
- An effective kinetic resolution of racemic α-arylpropanoic acids, α-arylbutanoic acids, and β-substituted-α-arylpropanoic acids with bis(9-phenanthryl)methanol as a new achiral nucleophile in the asymmetric esterification using carboxylic anhydrides and the acyl-transfer catalyst
-
A general method for the kinetic resolution of racemic α-arylalkanoic acids with achiral alcohols is described. It was determined that bis(9-phenanthryl)methanol is a suitable nucleophile which reacts with the intermediary mixed anhydrides generated from aromatic anhydrides with α-arylpropanoic acids or β-substituted-α-arylpropanoic acids in the presence of (+)-benzotetramisole to produce the corresponding optically active esters with high ee's under very mild conditions.
- Nakata, Kenya,Onda, Yu-Suke,Ono, Keisuke,Shiina, Isamu
-
experimental part
p. 5666 - 5669
(2010/11/18)
-
- Kinetic resolution of racemic α-arylalkanoic acids with achiral alcohols via the asymmetric esterification using carboxylic anhydrides and acyl-transfer catalysts
-
A variety of optically active carboxylic esters are produced by the kinetic resolution of racemic α-substituted carboxylic acids using achiral alcohols, aromatic or aliphatic carboxylic anhydrides, and chiral acyl-transfer catalysts. The combination of 4-methoxybenzoic anhydride (PMBA) or pivalic anhydride with the modified benzotetramisole-type catalyst ((S)-β-Np-BTM) is the most effective for promotion of the enantioselective coupling reaction between racemic carboxylic acids and a novel nucleophile, bis(α-naphthyl) methanol, to give the corresponding esters with high ees. This protocol was successfully applied to the production of nonracemic nonsteroidal anti-inflammatory drugs from racemic compounds utilizing the transacylation process to generate the mixed anhydrides from the acid components with the suitable carboxylic anhydrides.
- Shiina, Isamu,Nakata, Kenya,Ono, Keisuke,Onda, Yu-Suke,Itagaki, Makoto
-
supporting information; experimental part
p. 11629 - 11641
(2010/10/04)
-
- Iterative saturation mutagenesis accelerates laboratory evolution of enzyme stereoselectivity: Rigorous comparison with traditional methods
-
Efficacy in laboratory evolution of enzymes is currently a pressing issue, making comparative studies of different methods and strategies mandatory. Recent reports indicate that iterative saturation mutagenesis (ISM) provides a means to accelerate directed evolution of stereoselectivity and thermostability, but statistically meaningful comparisons with other methods have not been documented to date. In the present study, the efficacy of ISM has been rigorously tested by applying it to the previously most systematically studied enzyme in directed evolution, the lipase from Pseudomonas aeruginosa as a catalyst in the stereoselective hydrolytic kinetic resolution of a chiral ester. Upon screening only 10 000 transformants, unprecedented enantioselectivity was achieved (E = 594). ISM proves to be considerably more efficient than all previous systematic efforts utilizing error-prone polymerase chain reaction at different mutation rates, saturation mutagenesis at hot spots, and/or DNA shuffling, pronounced positive epistatic effects being the underlying reason.
- Reetz, Manfred T.,Prasad, Shreenath,Carballeira, Jose D.,Gumulya, Yosephine,Bocola, Marco
-
experimental part
p. 9144 - 9152
(2010/08/21)
-
- Directed evolution of an enantioselective lipase with broad substrate scope for hydrolysis of α-substituted esters
-
A variant of Candida antarctica lipase A (CalA) was developed for the hydrolysis of α-substituted p-nitrophenyl esters by directed evolution. The E values of this variant for 7 different esters was 45-276, which is a large improvement compared to 2-20 for the wild type. The broad substrate scope of this enzyme variant is of synthetic use, and hydrolysis of the tested substrates proceeded with an enantiomeric excess between 95-99%. A 30-fold increase in activity was also observed for most substrates. The developed enzyme variant shows (R)-selectivity, which is reversed compared to the wild type that is (S)-selective for most substrates.
- Engstroem, Karin,Nyhlen, Jonas,Sandstroem, Anders G.,Baeckvall, Jan-E.
-
supporting information; experimental part
p. 7038 - 7042
(2010/07/05)
-
- Homobenzotetramisole-catalyzed kinetic resolution of α-Aryl-, α-Aryloxy-, and α-Arylthioalkanoic acids
-
Effective kinetic resolutions of α-aryl-, αaryloxy-, and α-arylthioalkanoic acids have been achieved via in situ generation of their symmetrical anhydrides and enantioselective alcoholysis in the presence of homobenzotetramisole (HBTM) 3.
- Yang, Xing,Birman, Vladimir B.
-
supporting information; experimental part
p. 2301 - 2304
(2010/01/19)
-
- Catalytic asymmetric hiyama cross-couplings of racemic α-bromo esters
-
The first catalytic asymmetric cross-coupling of α-halo carbonyl compounds with aryl metal reagents has been developed, thereby generating synthetically useful α-aryl carboxylic acid derivatives in good enantiomeric excess. The method can also be applied to enantioselective alkenylation reactions. Copyright
- Dai, Xing,Strotman, Neil A.,Fu, Gregory C.
-
p. 3302 - 3303
(2008/10/09)
-
- Resolution of racemic 12-hydroxyl-1,15-pentadecanlactam using d-glucose derivative as a chiral auxiliary
-
Racemic 12-hydroxyl-1,15-pentadecanlactam 2 was resolved using glucose as a chiral auxiliary for the first time. Both the (R)- and (S)-isomers were obtained in high enantiomeric excesses (>99% by HPLC). The absolute configuration of (+)-2b and (-)-2a was determined by Horeau's method and a modified Mosher's method.
- Hou, Chuan-Jin,Liang, Xiao-Mei,Wu, Jing-Ping,Huang, Jia-Xing,Zhang, Jian-Jun,Wang, Dao-Quan
-
p. 379 - 383
(2008/09/19)
-
- Catalytic asymmetric synthesis of esters from ketenes
-
By building on elementary principles of Bronsted acid-base chemistry, a nucleophile-catalyzed method for the asymmetric synthesis of esters from ketenes has been transformed into a much more versatile and effective Bronsted acid-catalyzed process. The product aryl esters can be converted into useful derivatives, such as enantioenriched alcohols and carboxylic acids. Copyright
- Wiskur, Sheryl L.,Fu, Gregory C.
-
p. 6176 - 6177
(2007/10/03)
-
- Catalytic asymmetric couplings of ketenes with aldehydes to generate enol esters
-
(Chemical Equation Presented) With a little help from the ferrocenyl catalyst ((-)-1), a wide array of α-arylalkanoic acid derivatives can be produced from the catalytic asymmetric coupling of ketenes with aldehydes (see scheme). The enol esters are readily transformed into other useful families of compounds such as carboxylic acids and alcohols.
- Schaefer, Carsten,Fu, Gregory C.
-
p. 4606 - 4608
(2007/10/03)
-
- An efficient procedure for the resolution of α-cyano-α-fluoro- p-tolylacetic acid (CFTA) via the diastereomeric N-carbobenzyloxy-cis-1-amino-2- indanol esters
-
Development of a new, efficient resolution method of α-cyano-α- fluoro-p-tolylacetic acid (CFTA) 2a has been successfully achieved, which has been troublesome to obtain by conventional methods, in spite of its outstanding ability as an NMR chiral derivatizing agent. Fractional recrystallization of a mixture of the diastereomeric CFTA esters prepared from racemic CFTA chloride and (1R,2S)-N-carbobenzyloxy-cis-1-amino-2-indanol (-)-B afforded the less-soluble diastereomer, which was hydrolyzed to give (S)-2a. It has also been demonstrated that optically active N-acetyl-cis-1-amino-2-indanol is effective for the chromatographic resolution of α-arylacetic acids including ibuprofen and naproxen.
- Fujiwara, Tomoya,Sasaki, Masaki,Omata, Kenji,Kabuto, Chizuko,Kabuto, Kuninobu,Takeuchi, Yoshio
-
p. 555 - 563
(2007/10/03)
-
- Rational design of CH/π interaction sites in a basic resolving agent
-
A novel synthetic basic resolving agent, cis-1-aminobenz[f]indan-2-ol (ABI), was rationally designed by introducing effective CH/π interaction sites to cis-1-aminoindan-2-ol (AI), whose chiral recognition ability has been reported from our laboratory. ABI was applicable to a wide variety of racemic arylalkanoic acids and showed moderate to excellent chiral recognition ability, which was obviously higher than that of AI. The fundamental and important role of CH/π interactions, such as tunable CH(sp2)/π and CH(sp 3)/π interactions, in the chiral recognition by ABI was revealed by X-ray crystallographic study.
- Kobayashi, Yuka,Kurasawa, Toshie,Kinbara, Kazushi,Saigo, Kazuhiko
-
p. 7436 - 7441
(2007/10/03)
-
- Enantioselective hydrolysis of various racemic α-substituted arylacetonitriles using Rhodococcus sp. CGMCC 0497
-
The enantioselective hydrolysis of 17 racemic α-substituted arylacetonitriles by Rhodococcus sp. CGMCC 0497 is described. The corresponding (R)-amides and (S)-acids were obtained with excellent enantiomeric excess in most cases. The effect of steric and electronic factors on the outcome of the reactions are discussed here. The results prove that nitrile-converting enzymes are efficient tools for the synthesis of sterically unencumbered chiral α-arylpropionic acids and amides.
- Wu, Zhong-Liu,Li, Zu-Yi
-
p. 3305 - 3312
(2007/10/03)
-
- Diethyl zinc catalyzed diastereoselective addition of ketenes to (S)-(+)-3-hydroxytetrahydrofuran
-
The reaction of (S)-(+)-3-hydroxytetrahydrofuran with phenyl methyl ketene in presence of n-BuLi and Et2Zn results in the formation of the diastereomeric esters (SS+SR) with a high degree of diastereoselectivity (98:2).
- Tandon, Vishnu K.
-
p. 5985 - 5987
(2007/10/03)
-
- Enantioselective biotransformations of racemic α-substituted phenylacetonitriles and phenylacetamides using Rhodococcus sp. AJ270
-
Rhodococcus sp. AJ270 is an efficient whole-cell system able to catalyze the stereoselective conversions of racemic α-substituted phenylacetonitriles and amides under very mild conditions into enantiopure carboxylic acids and derivatives. The nitrile hydratase involved generally has a broad substrate spectrum against phenylacetonitriles irrespective of the electronic nature of the α-substituent while the amidase is very sensitive to both the electronic and steric factors of the substituent of amides. The overall enantioselectivity of nitrile hydrolysis is mainly determined by the combination of selectivities of nitrile hydratase and of amidase, with the latter being a major contributor. The amidase has high S-enantiocontrol against amides while the nitrile hydratase exhibits low R-selectivity against nitriles. The scope and limitations of this enantioselective biotransformation process are discussed. Copyright (C) 2000 Elsevier Science Ltd.
- Wang, Mei-Xiang,Lu, Gang,Ji, Gai-Jiao,Huang, Zhi-Tang,Meth-Cohn, Otto,Colby, John
-
p. 1123 - 1135
(2007/10/03)
-
- Enantioselective protonation of silyl enol ethers and ketene disilyl acetals with Lewis acid-assisted chiral Bronsted acids: Reaction scope and mechanistic insights
-
Enantioselective protonation is a potent and efficient way to construct chiral carbons. Here we report details of the reaction using Lewis acid-assisted chiral Bronsted acids (chiral LBAs). The 1:1 coordinate complex of tin tetrachloride and optically active binaphthol ((R)- or (S)-BINOL) can directly protonate various silyl enol ethers and ketene disilyl acetals to give the corresponding α-aryl ketones and α-arylcarboxylic acids, respectively, with high enantiomeric excesses (up to 98% ee). A catalytic version of enantioselective protonation has also been achieved using stoichiometric amounts of 2,6-dimethylphenol and catalytic amounts of monomethyl ether of optically active BINOL in the presence of tin tetrachloride. This protonation is also effective for producing α-halocarbonyl compounds (up to 91% ee). DFT calculations on the B3LYP/LANL2DZ level show that the conformational structure of the chiral LBA and the orientation of activated proton on (R)-BINOLs are important for understanding the absolute stereochemistry of the products.
- Nakamura, Shingo,Kaneeda, Masanobu,Ishihara, Kazuaki,Yamamoto, Hisashi
-
p. 8120 - 8130
(2007/10/03)
-
- Chiral discrimination of 2-arylalkanoic acids by (1S,2R)-1-aminoindan-2-ol through the formation of a consistent columnar supramolecular hydrogen-bond network
-
Enantiopure cis-1-aminoindan-2-ol was selected as a basic resolving agent for racemic 2-arylalkanoic acids on the basis that its rigid cis-conformation would favor the formation of a supramolecular hydrogen-bonded column, in which chiral discrimination of the racemic carboxylate would occur. It was found that this amino alcohol possesses high resolving efficiency for a variety of racemic acids; also, X-ray crystallographic analyses of the diastereomeric salts showed that a columnar hydrogen-bond network is formed in both the less- and more-soluble diastereomeric salts, as we had expected. A detailed study on the stabilising interactions suggested that there are two that play an important role: (i) hydrogen bonding between the ammonium and hydroxy groups and the acid carboxylate, which determines the formation of the columnar network and (ii) CH...π, which influences the herringbone packing of the aromatic groups, implying that it also plays some role in chiral discrimination.
- Kinbara, Kazushi,Kobayashi, Yuka,Saigo, Kazuhiko
-
p. 111 - 119
(2007/10/03)
-
- Enantiospecific synthesis of 4-(4'-methoxyphenyl)-hexan-3-one as precursor for optically active (pS) or (pR) isomer of (Z) or (E)-3-(2'-((N,N-dimethylamino)methylferrocenyl)-4-(4''-methoxyphenyl)-hex-3-ene
-
We describe herein an original method for the preparation of enantiomerically pure (Z)- or (E)-3-(2'-((N,N-dimethylamino)methylferrocenyl)-4-(4''-methoxyphenyl)-hex-3-ene possessing a p(S) or p(R) plane of chirality. The key step of the synthesis lies in obtaining enantiomerically pure (R) or (S) 4-(4'-methoxyphenyl)-hexan-3-one whose reaction with the lithiated N,N-dimethylaminomethylferrocene leads to two enantiomerically pure amino-alcohol diastereomers (pS,3S,4R) and (pR,3S,4R), or (pS,3R,4S) and (pR,3R,4S) respectively. Subsequent dehydration yields a mixture of three olefins, namely, two trisubstituted olefins and either the (Z)- or (E)-tetrasubstituted olefin with respect to the starting amino-alcohol diastereomer. Additionally we obtained the enantiomerically pure (R)- and (S)-4-phenyl-hexan-3-one and the corresponding diastereomeric amino-alcohols.
- Malezieux, Bernard,Gruselle, Michel,Troitskaya, Ludmila,Sokolov, Viatcheslav
-
p. 259 - 269
(2007/10/03)
-
- Pseudoephedrine as a practical chiral auxiliary for the synthesis of highly enantiomerically enriched carboxylic acids, alcohols, aldehydes, and ketones
-
The use of pseudoephedrine as a practical chiral auxiliary for asymmetric synthesis is described in full. Both enantiomers of pseudoephedrine are inexpensive commodity chemicals and can be N-acylated in high yields to form tertiary amides. In the presence of lithium chloride, the enolates of the corresponding pseudoephedrine amides undergo highly diastereoselective alkylations with a wide range of alkyl halides to afford α-substituted products in high yields. These products can then be transformed in a single operation into highly enantiomerically enriched carboxylic acids, alcohols, aldehydes, and ketones.
- Myers, Andrew G.,Yang, Bryant H.,Chen, Hou,McKinstry, Lydia,Kopecky, David J.,Gleason, James L.
-
p. 6496 - 6511
(2007/10/03)
-
- Synthesis of compounds with predetermined chirality
-
A method for synthesizing enantiomerically enriched chemical intermediates with predetermined chirality is described. The method comprises formation of a pseudoephedrine amide, followed by stereoselective alkylation at the alpha carbon. The chiral auxiliary can then be cleaved off, affording chiral end products useful for further transformations. The enantiomeric enrichment of the chiral end products may exceed 98%, and the chiral auxiliary can be recovered. Novel amides of pseudoephedrine used in this method are also disclosed.
- -
-
-
- Deracemization of α-substituted arylacetic acids
-
Reaction of rac-α-substituted arylacetyl chlorides with (R)- and (S)-3-hydroxy-4,4-dimethyl-1-phenyl-2-pyrrolidinone under standard esterification conditions, gave esters (3R,αR)- and (3S,αS)-3, respectively, with a diastereoselectivity which diminishes on increasing the steric effect of the α-substituent. Controlled acidic hydrolysis of esters 3 afforded the corresponding acids 4 with minimal racemization. Boron tribromide demethylation of (R)- and (S)-4d gave without racemization the hydroxyacids (R)- and (S)-4e, known precursors of (R)- and (S)-iodoalphionic acid.
- Camps, Pelayo,Gimenez, Silvia
-
p. 1227 - 1234
(2007/10/03)
-
- Stereoselective Hydrolysis of Nitriles and Amides Under Mild Conditions Using a Whole Cell Catalyst
-
An immobilised whole cell Rhodococcus sp. (SP 361) has been shown to be an effective catalyst for the stereoselective hydrolysis of both racemic and prochiral nitrile containing compounds. 2-Alkyl-arylacetonitriles 6a-8a were hydrolysed to (S)-acids and (R)-amides whereas the closely related substrate 9a gave the (R)-acid.A series of prochiral dinitriles 10a-13a were hydrolysed to the corresponding (S)-acids with e.e.'s 22-84percent.Models to account for the stereoselectivity of the enzymic hydrolyses have been proposed.
- Beard, Timothy,Cohen, Mark A.,Parratt, Julian S.,Turner, Nicholas J.,Crosby, John,Moilliet, Jock
-
p. 1085 - 1104
(2007/10/02)
-
- Enantioselective hydrolysis of nitriles and amides using an immobilised whole cell system
-
An immobilised whole cell catalyst SP361 has been shown to hydrolyse a range of 2-alkyl arylacetonitriles 1a-3a and amides 2b, 3b with good to excellent enantioselectivity. The absolute configuration of the derived amides and/or carboxylic acids shows remarkable changes according to the structure of the nitrile substrate.
- Cohen,Parratt,Turner
-
p. 1543 - 1546
(2007/10/02)
-
- Kinetic Resolution of Racemic Carboxylic Acids and Alcohols with Homochiral Alcohols and Carboxylic Acids, Respectively, and the Mukaiyama or Palomo Reagents
-
The Mukaiyama and Palomo reagents have been used for the kinetic resolution of racemic carboxylic acids or alcohols with homochiral alcohols or carboxylic acids, respectively, in the presence of triethylamine.Thus, enantiomerically enriched carboxylic acids (e.e.68percent), alcohols (e.e.41percent) or diastereoisomerically enriched esters (d.e.84percent) are obtained.
- Mazon, Angel,Najera, Carmen,Yus, Miguel,Heumann, Andreas
-
p. 1455 - 1466
(2007/10/02)
-
- Kinetic resolution of racemic carboxylic acids with homochiral alcohols and dicyclohexylcarbodiimide
-
Racemic carboxylic acids have been kinetically resolved by means of homochiral alcohols using the DCC-esterification methodology. The best results were obtained with commercially available homochiral 1-(4-pyridyl)ethanol: 60% e.e. for enantiomerically enriched acids and 76% d.e. for diastereomerically enriched esters.
- Chinchilla,Najera,Yus,Heumann
-
p. 101 - 104
(2007/10/02)
-
- DETERMINING THE ABSOLUTE CONFIGURATION OF HINDERED SECONDARY ALCOHOLS - A MODIFIED HOREAU'S METHOD
-
The kinetic resolution of racemic 2-phenylbutyryl chloride by hindered chiral secondary alcohols has been shown to be a viable approach to the determination of the absolute configuration of secondary alcohols through a study of ten chiral alcohols.
- Barnekow, David E.,Cardellina, John H.
-
p. 3629 - 3632
(2007/10/02)
-
- ENZYMATIC RESOLUTION OF METHYL 2-ALKYL-2-ARYLACETATES
-
Horse liver esterase, used as its inexpensive commercial acetone powder, catalyzes the selective hydrolysis of methy 2-alkyl-2-arylacetates to afford R(-)-2-alkyl-2-arylacetic acids and S(+)-methyl 2-alkyl-2-arylacetates.
- Ahmar, M.,Girard, C.,Bloch, R.
-
p. 7053 - 7056
(2007/10/02)
-
- COORDINATIVELY INDUCED 1,4-DIASTEREOSELECTION IN THE REACTION OF ACYCLIC α,β-ENONES WITH ORGANOCOPPER REAGENTS. A NEW TYPE OF ORGANOCOPPER REAGENT
-
A test has been made of a stereochemical prediction for conjugate addition based on the intermediacy of d,?*-complexes in the reaction of organocopper reagents with α,β-enones.The chiral α,β-enone 7 has been synthesized and subjected to reaction with various methyl cuprate reagents.Under conditions favorable to lithium chelation to the α-alkoxycarbonyl system of 7, conjugate addition to 7 was found to proceed with high (13:1 to 33:1) 1,4-diastereoselectivity, the configuration of the major diastereomer being that predicted by the d,?*-complex model.A new and especially diastereoselective reagent has been generated by the reaction of LiCuMe2 with 0.3 equivalent of water, a possible structure for which is presented.
- Corey, E. J.,Hannon, Francis J.,Boaz, Neil W.
-
p. 545 - 556
(2007/10/02)
-
- SYNTHESE ET PROPRIETES DES DEUX FORMES ENANTIOMERES DE POLY(THIOPHENES) CHIRAUX
-
Chiral poly(thiophenes) obtained from two enantiomerically pure monomers can stereoselectively recognize anions used as doping agents during voltammetric cycles.
- Lemaire, M.,Delabouglise, D.,Garreau, R.,Roncali, J.
-
p. 193 - 198
(2007/10/02)
-
- Direct Optical Resolution of Carboxylic Acids by Chyral HPLC on Tris(3,5-dimethylphenylcarbamate)s of Cellulose and Amylose
-
A variety of racemic carboxylic acids have been for the first time directly resolved by normal-phase, high-performance liquid chromatography using a hexane-2-propanol eluting system containing a small amount (ca. 1percent) of a strong carboxylic acid, like formic acid, trichloroacetic acid, and trifluoroacetic acid.
- Okamoto, Yoshio,Aburatani, Ryo,Kaida, Yuriko,Hatada, Koichi
-
p. 1125 - 1128
(2007/10/02)
-
- Enantioselective Chiral Poly(thiophenes)
-
Chiral poly(thiophenes) have been synthesized by electropolymerisation: they exhibit high specific rotation, stability, and conductivity and can stereoselectively recognize chiral anions used as doping agents during voltammetric cycles.
- Lemaire, Marc,Delabouglise, Didier,Garreau, Robert,Guy, Alain,Roncali, Jean
-
p. 658 - 661
(2007/10/02)
-
- Synthesis, Conformational Considerations, and Estrogen Receptor Binding of Diastereoisomers and Enantiomers of 1-phenyl>-1,2-diphenylbutane (Dihydrotamoxifen)
-
As part of a study into nonisomerizable antiestrogens, the diastereoisomeric dihydrotamoxifens 7 and 8 were prepared by catalytic transfer hydrogenation of (Z)- and (E)-tamoxifen and were shown by NMR spectrometry to exist in preferred conformations with hydrogen atoms in an antiperiplanar relationship.The corresponding 4-hydroxy derivatives 9 and 10 were prepared from hydrogenated precursors of (Z)- and (E)-4-hydroxytamoxifen.The relative binding affinities (RBA) of the compounds to estrogen receptors are consistent with the assigned conformations and parallel reported data on derivatives of the nonsteroidal estrogen hexestrol.The growth-inhibitory activity against the MCF-7 human breast cancer cell line in vitro was for 10 comparable to that of 4-hydroxytamoxifen, although increasing the concentration from 10-8 to 10-6 M did not significantly improve the growth inhibition.The derivative 9 analogous to (E)-4-hydroxytamoxifen antagonized the growth-stimulating effect of added estradiol and is therefore also an antiestrogen but at low concentration (10-8 M) in the absence of estradiol, MCF-7 cell growth was stimulated, indicating an estrogenic influence.The enantiomers of the dihydrotamoxifen 8 were individually prepared from the resolved enantiomers of 2-phenylbutanoic acid, the key reaction step being a lithium-ammonia reduction of the 1-(4-methoxyphenyl)-1,2-diphenyl-1-butanol to generate the triphenylbutane.The enantiomers of 8 gave identical RBA values in cytosol.
- McCague, Raymond,Leclercq, Guy
-
p. 1761 - 1767
(2007/10/02)
-
- Secondary Mould Metabolites. Part 16. Stemphyltoxins, New Reduced Perylenequinone Metabolites from Stemphylium botryosum var. Lactucum
-
The structure and stereochemistry of stemphyltoxins I-IV (1)-(4), four epoxy derivatives of reduced perylenequinones isolated from the fungus Stemphylium botryosum var.Lactucum, have been elucidated, mainly on the basis of n.m.r. evidence.A further metabolite, stemphyperylenol (5), is a hexahydro-1,4,7,10-tetrahydroxyperylene-3,9-quinone, a structure which suggests an unusual head-to-tail biosynthetic coupling of two pentaketide units.
- Arnone, Alberto,Nasini, Gianiuca,Merlini, Lucio,Assante, Gemma
-
p. 525 - 530
(2007/10/02)
-
- Optical Resolution of 1-Hydroxyethylphosphinic Acid and Its Esters
-
Both enantiomers of 1-hydroxyethylphosphinic acid were obtained by resolution of the racemic acid using (+)- and (-)-1-(1-naphthyl)ethylamine as the resolving agents, and the (+)-isomer was assigned to be (S)-configuration.The four diastereomers of butyl 1-hydroxyethylphosphinates were prepered in an optically pure state by reacting the resolved acid with 1-butanol in benzene and then separating the diastereomeric products by chromatographic means.
- Sasaki, Mitsuru
-
p. 741 - 746
(2007/10/02)
-
- Tremorgenic Mycotoxins from Penicillium crustosum: Isolation of Penitrems A-F and the Structure Elucidation and Absolute Configuration of Penitrem A
-
The isolation and characteristics of six tremorgenic mycotoxins, penitrems A-F from cultures of Penicillium crustosum are reported.The assignment of structure (2) to penitrem A is based on a detailed study of its high-field 1H and 13C n.m.r. spectra.The conformation and relative configuration of penitrem A was deduced from the observed proton-proton nuclear Overhauser effects (n.O.e) and the magnitude of the proton-proton coupling constants.The chirality of C-25 was determined as S by the 'partial resolution' method of Horeau and penitrem A must therefore have the (12R, 14S, 15R, 18S,19R, 22S, 23S, 24R, 25S, 26R, 28S, 31R, 32S) absolute configuration.
- Jesus, Amelia E. de,Steyn, Pieter S.,Heerden, Fanie R. van,Vleggaar, Robert,Wessels, Philippus L.,Hull, William E.
-
p. 1847 - 1856
(2007/10/02)
-