- Effects of organic solvents and ionic liquids on the aminolysis of (RS)-methyl mandelate catalyzed by lipases
-
The enzymatic resolution of (RS)-methyl mandelate with n-butylamine using lipases in organic solvents (n-hexane, tert-butanol, and chloroform) and ionic liquids [BMIm][BF4] and [BMIm][PF6] is reported. The amide configuration is dependent on the organic solvent. When using mixtures of chloroform or tert-butanol/ionic liquids (10:1 v/v) with CAL-B as the catalyst, the amides were obtained in high enantiomeric excess (eep >99% and E >200).
- Pilissao, Cristiane,Nascimento, Maria Da Graca
-
-
Read Online
- Supramolecular crystalline construction based on a mandelic acid source. host design, inclusion formation and X-ray crystal structures of a methanol inclusion complex and free host structures in racemic and optically resolved forms
-
A new host compound in optically resolved and racemic forms for selective crystalline inclusion formation derived from natural mandelic acid was synthesized. Inclusion properties of the two optical species are discussed, involving comparison with a lactic acid-based host analogue. Inclusion compounds with amines, ketones and heterocyclics and specifically with small unbranched alcohols were isolated. The crystal and molecular structures of the optically resolved and racemic forms of the free host at room temperature and the methanol inclusion complex of the resolved host at 255 K were determined by x-ray analysis. Two different binding schemes characterize the packing of these structures, in which one hydroxyl group is responsible for the formation of dimers and chains while in the free host the other hydroxyl group is involved in OH-phenyl interactions. A survey of the OH...phenyl interactions based on the Cambridge Structural Data Base (October 1994 version) reveals that π-electron bonding occurs in a wide range of crystal structures. The approximation of the hydrogen appears to take place in an asymmetric way. Several calculations for the ab initio prediction of the crystal structures were performed.
- Weber, Edwin,Hager, Orm,Foces-Foces, Concepcion,Llamas-Saiz, Antonio L.
-
-
Read Online
- New data to the origin of rate enhancement on the Pt-cinchona catalyzed enantioselective hydrogenation of activated ketones using continuous-flow fixed-bed reactor system
-
A study on the origin of rate enhancement (RE) in the enantioselective heterogeneous catalytic hydrogenation of methyl benzoylformate (MBF), ketopantolactone (KPL) and pyruvic aldehyde dimethyl acetal (PA) under the Orito reaction conditions over Pt catalyst modified with parent cinchona alkaloids, as compared to the unmodified catalyst is presented. The hydrogenations were carried out in continuous-flow fixed-bed reactor system over 20-100 mg Pt/Al2O3 catalyst in 1 mL min-1 flow of toluene/acetic acid 9/1 solvent mixture under 40-80 bar H2 pressure, at 283 or 293 K using 0.044-2 mM modifier concentration and 45 mM substrate concentration. Our results obtained using racemic hydrogenations followed by three changes of the chiral modifier (on the same catalyst) supported the so-called "ligand acceleration" phenomenon in the enantioselective hydrogenation of activated ketones such as MBF, KPL and PA. In our opinion, RE produced by the first modifier added after racemic hydrogenation can also be explained by the purifying effect of the cinchona. REs observed following further exchanges of modifiers are indicative of the intrinsic character of the phenomenon. This research suggested that the origin of enantiodifferentiation and rate enhancement is the same, namely, both may be traced back-probably in different ways-to the role of the intermediate complexes of the hydrogenation, to its formation and transformation, which in turn depends on numerous factors.
- Szoellosi, Gyoergy,Cserenyi, Szabolcs,Fueloep, Ferenc,Bartok, Mihaly
-
-
Read Online
- REDUCTIONS WITH NADH MODELS II: ASYMMETRIC INDUCTION WITH SUGAR SUBSTITUTED HANTZSCH ESTERS OR WITH CHIRAL LEWIS ACIDS
-
Hantzsch esters 3 and 4 have been used as NADH models instead of the well documented nicotinamides 1 for the sake of greater flexibility in the preparation and chemical modifications.Compounds 3 and 4, bearing monosaccharide-derived substituents in the 4- or in both the 3- and 5- positions were examined in the asymmetric reduction of several prochiral ketones: namely methyl phenylglyoxylate, trifluoroacetophenone and 2-acetyl pyridine.The e.e. 's obtained are discussed in terms of the structure of the sugar residue and its position on the dihydropyridine ring.The effects of Mg2+ catalysis is discussed and the possibility of using others Lewis acids - especially chiral ones - is examined.
- Zehani, Sadek,Lin, Jian,Gelbard, Georges
-
-
Read Online
- Enantiocomplementary preparation of (S)- and (R)-mandelic acid derivatives via α-hydroxylation of 2-arylacetic acid derivatives and reduction of α-ketoester using microbial whole cells
-
Forty one microorganisms belonging to different taxonomical groups were used to carry out the enantioselective reduction of methyl benzoylformate to afford the corresponding (R)-methyl mandelate, with moderate to high ee. In contrast, the monooxygenase en
- Chen, Yongzheng,Xu, Jinggang,Xu, Xiaoying,Xia, Yu,Lin, Hui,Xia, Shiwen,Wang, Lixin
-
-
Read Online
- A new type of NADH model compound: Synthesis and reactions
-
Four diastereomeric NADH model compounds were synthesized by the reaction of a pinyl substituted Hantzch ester with dimethylaluminum amide. The reduction of methyl benzoylformate with these models gave both enantiomers of methyl mandelate
- Li, Xianfeng,Tanner, Dennis D.
-
-
Read Online
- Effect of the neighbouring oxygenated substituent on asymmetric reduction with Hantzsch-type 1,4-dihydropyridines having a chiral sulfinyl group
-
Introduction of the oxygen substituent at C-6 of the Hantzsch-type compound having a sulfinyl group at C-5 affects the reduction of ketones with respect to both reactivity and stereoselectivity.
- Miyashita, Kazuyuki,Nishimoto, Masahiro,Murafuji, Hidenobu,Murakami, Asuka,Obika, Satoshi,In, Yasuko,Ishida, Toshimasa,Imanishi, Takeshi
-
-
Read Online
- Novel silica gel supported chiral biaryl-diphosphine ligands for enantioselective hydrogenation
-
The synthesis of functionalized Biphemp and MeO-Biphep biaryl diphosphine ligands and their covalent attachment to silica gel are described. The catalytic performance of the immobilized ligands was tested in the asymmetric hydrogenation of methyl acetamid
- Steiner, Ivo,Aufdenblatten, Rhony,Togni, Antonio,Blaser, Hans-Ulrich,Pugin, Benoit
-
-
Read Online
- Asymmetric reduction of α-keto esters with Thermus thermophilus NADH-dependent carbonyl reductase using glucose dehydrogenase and alcohol dehydrogenase for cofactor regeneration
-
The enantioselective synthesis of methyl (R)-mandelate and methyl (R)-o-chloromandelate was investigated using an NADH-dependent carbonyl reductase from Thermus thermophilus (TtADH) and, separately, archaeal glucose dehydrogenase and Bacillus stearothermo
- Pennacchio, Angela,Giordano, Assunta,Rossi, Mose,Raia, Carlo A.
-
-
Read Online
- The Enzyme/Coenzyme/Metal/Substrate Quaternary Complex Generated in the Transition State of the Reduction of Benzoylformate with NAD(P)H Models
-
Enantioselectivities in the reduction of methyl benzoylformate with NAD(P)H model compounds, N-α-methylbenzyl-1-propyl-1,4-dihydronicotinamide (PNPH) and N-benzyl-1-propyl-1,4-dihydronicotinamide (PNBH), in the presence of N-protected amino acids have bee
- Mikata, Yuji,Mizukami, Kiyoko,Ikehara, Kenji,Ohno, Atsuyoshi
-
-
Read Online
- Substrate-controlled adsorption of cinchonidine during enantioselective hydrogenation on platinum
-
It is commonly accepted that the origin of enantioselection on chirally modified metals is the control of the adsorption and reactivity of the substrate by the chiral environment of the modifier. Here, we provide the first experimental evidence to a mutual process, namely, that the substrate controls the adsorption and reactivity of cinchonidine (CD) on the metal surface. Our approach is to follow the competing hydrogenation of the quinoline ring, the anchoring moiety of CD, in the presence or absence of an activated ketone substrate. On Pt/Al2O3 in the weakly interacting solvent toluene, CD (and 10,11-dihydro-CD) favors a C(4′) - pro(S) adsorption geometry and saturation of the heteroaromatic ring gives 1′,2′, 3′,4′(S),10,11-hexahydro-CD {(S)-CDH6} in excess. Addition of methyl benzoylformate, ketopantolactone, or ethyl pyruvate inverts the dominant conformation of CD to C(4′) - pro(R) as indicated by the major product (R)-CDH6, and even the rate is higher by about 30% ("inverse ligand acceleration"). Acetic acid that interacts strongly with CD exerts a similar effect on quinoline hydrogenation. In contrast, the product α-hydroxyester interacts weakly with CD, decelerates the hydrogenation of the quinoline ring and the de of CDH6 depends on the chirality of the α-hydroxyester. These unexpected observations provide a fundamentally new insight into the complexity of the surface conformation of CD and the origin of high enantioselectivity on cinchona-modified Pt.
- Schmidt, Erik,Mallat, Tamas,Baiker, Alfons
-
-
Read Online
- Additional data to the origin of rate enhancement in the enantioselective hydrogenation of activated ketones over cinchonidine modified platinum catalyst
-
Kinetic behaviour of different substrates such as purified ethyl pyruvate, dimer containing (20%) ethyl pyruvate, methylbenzoyl formate and ketopantolactone was investigated in both racemic and enantioselective hydrogenation over Pt/Al2O3 catalysts. Upon introducing the chiral modifier by injection under condition of racemic hydrogenation an immediate increase in reaction rate is observed in the case of all substrates. Consequently, significant rate enhancement (RE) was obtained in the case of all substrates. The RE increased in the following order: ketopantolactone ethyl pyruvate methylbenzoyl formate. This order does not follow the ability of substrates to be involved in various undesired side reactions with the formation of poisonous surface residues. Accordingly, results obtained in this study confirm that the RE must be an intrinsic feature of the asymmetric hydrogenation of activated ketones in the presence of cinchona alkaloids. However, our results also indicate that the poisoning effect by organic residues originated from ethyl pyruvate cannot be neglected.
- Talas, Emilia,Margitfalvi, Jozsef L.,Egyed, Orsolya
-
-
Read Online
- Kinetic resolutions of racemic amines and alcohols catalyzed by an industrial glutaryl-7-aminocephalosporanic acid acylase with unexpected broad substrate specificity
-
An industrial glutaryl-7-aminocephalosporanic acid acylase (GAR) possesses a significant broad substrate specificity that crosses over the usual cephalosporanic skeleton. Enantioselective amidase and even esterase activities have been observed with all the glutarates of racemic substrates investigated, with a stereopreference for the (S)-enantiomer. The different physical-chemical properties of reagents and products allow their easy separation by solvent extraction, avoiding cumbersome chromatography or distillation processes during reaction work-up.
- Raimondi, Stefano,Forti, Luca,Monti, Daniela,Riva, Sergio
-
-
Read Online
- Highly enantioselective reduction with novel, bridged NADH models
-
Biomimetic reduction of benzoylformate to mandelate with 97-99% ee was achieved with the diastereomeric, bridged NADH models (S.S)-1 and (R.S)-1. The oligomethylene bridge acts as an 'enzyme wall' and hinders the approach of the substrate from one side of
- Kanomata,Nakata
-
-
Read Online
- Rational design of novel axially chiral NADH models based on configurational control of atropisomeric lactams
-
The preparation of a new class of axially chiral NADH models based on configurational control of atropisomeric lactams is described. The configurational control of this chiral axis is achieved via the presence of a second chirality element installed on th
- Vasse, Jean-Luc,Dupas, Georges,Duflos, Jack,Quéguiner, Guy,Bourguignon, Jean,Levacher, Vincent
-
-
Read Online
- Dynamic kinetic resolution of α-hydroxy acid Esters
-
Enzymatic resolution in combination with ruthenium-catalyzed racemization of the substrate led to dynamic kinetic resolution of α-hydroxy esters in good yields and excellent ee's. Studies of different parameters showed that the best results were obtained
- Huerta, Fernando F.,Laxmi, Y.R. Santosh,Baeckvall, Jan-E.
-
-
Read Online
- Homochiral NADH models in the pyrrolo[2,3-b]pyridine series bearing one or two chiral auxiliaries. Asymmetric reduction of methyl benzoylformate and N-acetyl-enamines. Influence of the magnesium salt concentration on the asymmetric induction of reductions
-
The synthesis of NADH models in the pyrrolo[2,3-b]pyridine series bearing one or two chiral auxiliaries either at the pyridine or at the pyrrole ring is described. These models were involved in the reduction of methyl benzoylformate. The reactivity of the
- Leroy, Corine,Levacher, Vincent,Dupas, Georges,Queguiner, Guy,Bourguignon, Jean
-
-
Read Online
- Catalytic, enantioselective [4 + 2]-cycloadditions of ketene enolates and o-quinones: Efficient entry to chiral, α-oxygenated carboxylic acid derivatives
-
We report catalytic, enantioselective [4 + 2]-cycloadditions of o-quinones with ketene enolates (derived from readily available acid chlorides) using cinchona alkaloid derivatives as catalysts to produce products in high enantiomeric excess (ee) and good
- Bekele, Tefsit,Shah, Meha H.,Wolfer, Jamison,Abraham, Ciby J.,Weatherwax, Anthony,Lectka, Thomas
-
-
Read Online
- Cationic complexes with chiral diamine or dithiourea ligands as catalysts for molecular asymmetric hydrogenation
-
The asymmetric reduction of phenylglyoxylate methyl ester with molecular hydrogen and catalytic amounts of cationic chiral diamine and dithiourea complexes of rhodium and iridium is reported. The catalytic activity of the complexes is rather different if
- Tommasino, M. Lorraine,Thomazeau, Cecile,Touchard, Francois,Lemaire
-
-
Read Online
- Potential of ionic liquids as co-modifiers in asymmetric hydrogenation on platinum
-
The enantioselective hydrogenation of methyl benzoylformate on Pt/Al 2O3 has been studied in the presence of various ionic liquids (ILs) and three structurally related chiral modifiers: cinchonidine (CD), O-phenyl-cinchonidine (PhOCD
- Sano, Shogo,Beier, Matthias Josef,Mallat, Tamas,Baiker, Alfons
-
-
Read Online
- Asymmetric Reductions catalysed by Chiral Shift Reagents
-
The reduction of methyl phenylglyoxylate to give optically active methyl mandelate by NADH models is catalysed by chiral shift reagents used as Lewis acids.
- Zehani, Sadek,Gelbard, Georges
-
-
Read Online
- Highly efficient chemoenzymatic synthesis of methyl (R)-o-chloromandelate, a key intermediate for clopidogrel, via asymmetric reduction with recombinant Escherichia coli
-
Methyl (R)-o-chloromandelate [(R)-1], which is an intermediate for a platelet aggregation inhibitor named clopidogrel, was obtained in >99% ee by the asymmetric reduction of methyl o-chlorobenzoylformate (2) with recombinant Escherichia coli overproducing
- Ema, Tadashi,Ide, Sayaka,Okita, Nobuyasu,Sakai, Takashi
-
-
Read Online
- Highly enantioselective and efficient synthesis of methyl (R)-o-chloromandelate with recombinant E. coli: Toward practical and green access to clopidogrel
-
Methyl (R)-o-chloromandelate ((R)-1), which is an intermediate for a platelet aggregation inhibitor named clopidogrel, was obtained in >99% ee by the asymmetric reduction of methyl o-chlorobenzoylformate (2) (up to 1.0 M) with recombinant E. coli overprod
- Ema, Tadashi,Okita, Nobuyasu,Ide, Sayaka,Sakai, Takashi
-
-
Read Online
- Organocatalytic conversion of arylglyoxals into optically active mandelic acid derivatives
-
A novel protocol for the organocatalytic conversion of arylglyoxals into the corresponding α-hydroxy arylacetic acid methyl esters has been developed. The catalyst consists of a combination of a commercially available cinchona alkaloid derivative and an a
- Schmitt, Ellen,Schiffers, Ingo,Bolm, Carsten
-
-
Read Online
- Atropoisomeric quinolinium salt promoting the access to both enantiomeric forms of methyl mandelate: a versatile NADH mimic.
-
Asymmetric reduction of methyl benzoylformate by a new NADH mimic is reported; depending on the hydride source used to reduce the NAD+ precursor, NADH mimics so obtained lead to an inversion of enantioselectivity, affording either (R)-methyl mandelate in
- Vasse, Jean-Luc,Levacher, Vincent,Bourguignon, Jean,Dupas, Georges
-
-
Read Online
- Highly reactive and stereospecific reaction of quinoline-type NADH model compounds with methyl benzoylformate
-
NADH model compounds with a dihydroquinoline ring can reduce methyl benzoylformate with very high reactivity and stereospecificity. Chiral column HPLC is effective in the separation and analysis of enantiomers of NADH and NAD model compounds, respectively. (C) 2000 Elsevier Science Ltd.
- Mikata, Yuji,Hayashi, Kayo,Mizukami, Kiyoko,Matsumoto, Sawako,Yano, Shigenobu,Yamazaki, Norimasa,Ohno, Atsuyoshi
-
-
Read Online
- A Novel Coenzyme NAD(P)+ - NAD(P)H Model with Axial Chirality. Its Preparation and Stereoselectivity.
-
An axially chiral NAD(P)H model 1 bearing a 2'-methoxy-1'-naphthyl group at the C-2 position is prepared; the reduction of methyl benzoylformate with the optically active model, (+)- or (-)-1, in the presence of magnesium ion gives (R)- or (S)-isomer of m
- Fujii, Masayuki,Kamata, Tohru,Okamura, Mutsuo,Ohno, Atsuyoshi
-
-
Read Online
- Constraining Asymmetric Organometallic Catalysts within Mesoporous Supports Boosts Their Enantioselectivity
-
By constraining tethered asymmetric organometallic catalysts within the nanopores of silica supports so as to increase the interaction between the pore wall and the active center (and hence to restrict access of the reactant to the catalyst), a significan
- Raja, Robert,Thomas, John Meurig,Jones, Matthew D.,Johnson, Brian F. G.,Vaughan, David E. W.
-
-
Read Online
- Catalytic, asymmetric inverse electron demand hetero diels-alder reactions of o-benzoquinone derivatives and ketene enolates
-
We present an array of [4+2] cycloaddition reactions between ketene enolates, catalytically derived from acid chlorides and cinchona alkaloid nucleophilic catalysts in the presence of stoichiometric base, and o-benzoquinone derivatives. These cycloadditio
- Paull, Daniel H.,Wolfer, Jamison,Grebinski, James W.,Weatherwax, Anthony,Lectka, Thomas
-
-
Read Online
- New data on enantiomeric excess versus conversion during enantioselective hydrogenation of activated ketones on a platinum catalyst
-
The initial transient period (ITP) was studied in the enantioselective hydrogenation of activated ketones (ethyl pyruvate, pyruvaldehyde dimethyl acetal, methyl benzoyl formate) on Pt-alumina (E4759) catalyst modified by cinchonidine (CD) or dihydrocincho
- Balazsik, Katalin,Bartok, Mihaly
-
-
Read Online
- Construction of homochiral alkaline-lanthanide heteronuclear helicates with Na+-selective bonding in the self-assembly process
-
A supramolecular approach to distinguish Na+ from other biologically important metal ions was demonstrated. By designing ligands reasonably, Na+-selective bonding was achieved in the construction of homochiral alkaline-lanthanide het
- Li, Ge,Wang, Li,Han, Qingxin,Liu, Weisheng
-
-
Read Online
- Pseudomonas sp. lipase immobilized in polymers versus the use of free enzyme in the resolution of (R,S)-methyl mandelate
-
In the present report, we describe the preparative-scale resolution of (R,S)-methyl mandelate by acylation with vinyl acetate catalyzed by free Pseudomonas sp. lipase or immobilized in poly(ethylene) oxide (PEO) and agar gel, in organic media. Under exper
- Queiroz, Neide,Nascimento, Mariada Gra?a
-
-
Read Online
- N-methyl-(R)-3-(tert-butyl)-sulfinyl-1,4-dihydropyridine: A novel NADH model compound
-
We have synthesized a novel chiral NADH model compound, N-methyl-(R)-3-(tert-butyl)-sulphinyl-1,4-dihydropyridine with high enantioselectivity and used it in the reduction of methyl benzoylformate, producing (S)-methyl mandelate in 95% ee. The absolute st
- Xie, Kun,Liu, You-Cheng,Cui, Yi,Wang, Jian-Ge,Fu, Yao,Mak, Thomas C. W.
-
-
Read Online
- 1,3-mandelic acid thioether derivative containing '4 - R/S - oxadiazole' structure and application thereof
-
1,3 Mandelic acid thioether compound containing the structure of '4 - R/S - oxadiazole' is characterized in that the structure is as shown in the general formula (In / IIn) and (In In-flight R1 A is H or Cl, R. 2 For linear alkanes C
- -
-
Paragraph 0021-0024
(2021/10/13)
-
- Biocatalysed reductions of α-ketoesters employing CyreneTM as cosolvent
-
The search for novel reaction media with environmental friendly properties is an area of great interest in enzyme catalysis. Water is the medium of biocatalysed processes, but due to its properties, sometimes the presence of organic (co)solvents is required. CyreneTM represents one of the newest approaches to this medium engineering. This polar solvent has been employed for the first time in biocatalysed reductions employing purified alcohol dehydrogenases. A set of α-ketoesters has been reduced to the corresponding chiral α-hydroxyesters with high conversions and optical purities, being possible to obtain good results at Cyrene contents of 30% v/v and working at substrate concentrations of 1.0 M in presence of 2.5% v/v of this solvent. At this concentration, the presence of Cyrene has a beneficial effect in the bioreduction conversion.
- de Gonzalo, Gonzalo
-
-
- Scalable On-Demand Production of Purified Diazomethane Suitable for Sensitive Catalytic Reactions
-
We have developed a convenient development-scale reactor (0.44 mol/h) to prepare diazomethane from N-methyl-N-nitroso-p-toluenesulfonamide (MNTS) in ~80% yield. Diazomethane (CH2N2) made with this reactor is extracted into nitrogen gas from the liquid reaction mixture, effectively removing it from reagents and byproducts that may interfere in subsequent reactions. Vertically oriented tubular reactors were used to produce and consume diazomethane in situ. Key features of this reactor include high productivity and correspondingly low reactor volume (reactor volume/liquid flow rate = 6.5 min) and a commercially available gas/liquid separator equipped with a selectively permeating hydrophilic membrane. The design of the reactor keeps the inventory below 53 mg of CH2N2 during normal operation. The reactor was demonstrated by generating CH2N2 that was used in a connected continuous reactor. We evaluated esterification reactions and a continuous Pd-catalyzed cyclopropanation reaction with the reactor and achieved high conversion with 1.5 and 4.1 equiv of MNTS precursor, respectively.
- Sheeran, Jillian W.,Campbell, Kiersten,Breen, Christopher P.,Hummel, Gerald,Huang, Changfeng,Datta, Anamika,Boyer, Serge H.,Hecker, Scott J.,Bio, Matthew M.,Fang, Yuan-Qing,Ford, David D.,Russell, M. Grace
-
supporting information
p. 522 - 528
(2021/02/03)
-
- Redox-driven deracemization of secondary alcohols by sequential ether/O2-mediated oxidation and Ru-catalyzed asymmetric reduction
-
The deracemization of benzylic alcohols has been achieved using a redox-driven one-pot two-step process. The racemic alcohols were oxidized by bis(methoxypropyl) ether and oxygen to give the ketone intermediates, followed by an asymmetric transfer hydrogenation with a chiral ruthenium catalyst. This compatible oxidation/reduction process gave the enantiomerically enriched alcohols with up to 95% ee values.
- Yang, Bing,Cui, Peng,Chen, Yongsheng,Liu, Qixing,Zhou, Haifeng
-
-
- Iridium-Catalyzed Enantioselective Transfer Hydrogenation of Ketones Controlled by Alcohol Hydrogen-Bonding and sp3-C?H Noncovalent Interactions
-
Iridium-catalyzed enantioselective transfer hydrogenation of ketones with formic acid was developed using a prolinol-phosphine chiral ligand. Cooperative action of the iridium atom and the ligand through alcohol-alkoxide interconversion is crucial to facilitate the transfer hydrogenation. Various ketones including alkyl aryl ketones, ketoesters, and an aryl heteroaryl ketone were competent substrates. An attractive feature of this catalysis is efficient discrimination between the alkyl and aryl substituents of the ketones, promoting hydrogenation with the identical sense of enantioselection regardless of steric demand of the alkyl substituent and thus resulting in a rare case of highly enantioselective transfer hydrogenation of tert-alkyl aryl ketones. Quantum chemical calculations revealed that the sp3-C?H/π interaction between an sp3-C?H bond of the prolinol-phosphine ligand and the aryl substituent of the ketone is crucial for the enantioselection in combination with O?H???O/sp3-C?H???O two-point hydrogen-bonding between the chiral ligand and carbonyl group. (Figure presented.).
- Murayama, Hiroaki,Heike, Yoshito,Higashida, Kosuke,Shimizu, Yohei,Yodsin, Nuttapon,Wongnongwa, Yutthana,Jungsuttiwong, Siriporn,Mori, Seiji,Sawamura, Masaya
-
supporting information
p. 4655 - 4661
(2020/07/13)
-
- Insights into the Substrate Promiscuity of Novel Hydroxysteroid Dehydrogenases
-
Hydroxysteroid dehydrogenases (HSDHs) are valuable biocatalysts for the regio- and stereoselective modification of steroids, bile acids and other steroid derivatives. In this work, we investigated the substrate promiscuity of this highly selective class of enzymes. In order to reach this goal, a preliminary search of HSDH homologues in in-house or public available (meta)genomes was carried out. Eight novel NAD(H)-dependent HSDHs, showing either 7α-, 7β-, or 12α-HSDH activity, and including, for the first time, enzymes from extremophilic microorganisms, were identified, recombinantly produced, and characterized. Among the novel HSDHs, four highly active (up to 92 U mg?1) NAD(H)-dependent 7β-HSDHs showing negligible similarity towards previously described 7β-HSDHs, were discovered. These enzymes, along with previously characterized HSDHs, were tested as biocatalysts for the stereoselective reduction of a panel of substrates including two α-ketoesters of pharmaceutical interest and selected ketones that partially resemble the structural features of steroids. All the reactions were coupled with a suitable cofactor regeneration system. Regarding the α-ketoesters, nearly all of the tested HSDHs showed a good activity toward the selected substrates, yielding the reduced α-hydroxyester with up to 99% conversions and enantiomeric excesses. On the other hand, only the 7β-HSDHs from Collinsella aerofaciens and Clostridium absonum showed appreciable activity toward more complex ketones, i. e., (±)-trans-1-decalone, but with interesting as well as different selectivity. (Figure presented.).
- Bertuletti, Susanna,Ferrandi, Erica Elisa,Marzorati, Stefano,Vanoni, Marta,Riva, Sergio,Monti, Daniela
-
p. 2474 - 2485
(2020/05/06)
-
- Exploiting Cofactor Versatility to Convert a FAD-Dependent Baeyer–Villiger Monooxygenase into a Ketoreductase
-
Cyclohexanone monooxygenases (CHMOs) show very high catalytic specificity for natural Baeyer–Villiger (BV) reactions and promiscuous reduction reactions have not been reported to date. Wild-type CHMO from Acinetobacter sp. NCIMB 9871 was found to possess an innate, promiscuous ability to reduce an aromatic α-keto ester, but with poor yield and stereoselectivity. Structure-guided, site-directed mutagenesis drastically improved the catalytic carbonyl-reduction activity (yield up to 99 %) and stereoselectivity (ee up to 99 %), thereby converting this CHMO into a ketoreductase, which can reduce a range of differently substituted aromatic α-keto esters. The improved, promiscuous reduction activity of the mutant enzyme in comparison to the wild-type enzyme results from a decrease in the distance between the carbonyl moiety of the substrate and the hydrogen atom on N5 of the reduced flavin adenine dinucleotide (FAD) cofactor, as confirmed using docking and molecular dynamics simulations.
- Xu, Jian,Peng, Yongzhen,Wang, Zhiguo,Hu, Yujing,Fan, Jiajie,Zheng, He,Lin, Xianfu,Wu, Qi
-
p. 14499 - 14503
(2019/09/17)
-
- Two enantiocomplementary ephedrine dehydrogenases from arthrobacter sp. TS-15 with broad substrate specificity
-
The recently identified pseudoephedrine and ephedrine dehydrogenases (PseDH and EDH, respectively) from Arthrobacter sp. TS-15 are NADH-dependent members of the oxidoreductase superfamily of short-chain dehydrogenases/reductases (SDRs). They are specific for the enantioselective oxidation of (+)-(S) N-(pseudo)ephedrine and (-)-(R) N-(pseudo)ephedrine, respectively. Anti-Prelog stereospecific PseDH and Prelog-specific EDH catalyze the regio- A nd enantiospecific reduction of 1-phenyl-1,2-propanedione to (S)-phenylacetylcarbinol and (R)-phenylacetylcarbinol with full conversion and enantiomeric excess of >99%. Moreover, they perform the reduction of a wide range of aryl-aliphatic carbonyl compounds, including ketoamines, ketoesters, and haloketones, to the corresponding enantiopure alcohols. The highest stability of PseDH and EDH was determined to be at a pH range of 6.0-8.0 and 7.5-8.5, respectively. PseDH was more stable than EDH at 25 °C with half-lives of 279 and 38 h, respectively. However, EDH is more stable at 40 °C with a 2-fold greater half-life than at 25 °C. The crystal structure of the PseDH-NAD+ complex, refined to a resolution of 1.83 ?, revealed a tetrameric structure, which was confirmed by solution studies. A model of the active site in complex with NAD+ and 1-phenyl-1,2-propanedione suggested key roles for S143 and W152 in recognition of the substrate and positioning for the reduction reaction. The wide substrate spectrum of these dehydrogenases, combined with their regio- A nd enantioselectivity, suggests a high potential for the industrial production of valuable chiral compounds.
- Shanati, Tarek,Lockie, Cameron,Beloti, Lilian,Grogan, Gideon,Ansorge-Schumacher, Marion B.
-
p. 6202 - 6211
(2019/08/15)
-
- Synergetic Organocatalysis for Eliminating Epimerization in Ring-Opening Polymerizations Enables Synthesis of Stereoregular Isotactic Polyester
-
Ring-opening polymerization of O-carboxyanhydrides (OCAs) can furnish polyesters with a diversity of functional groups that are traditionally hard to harvest by polymerization of lactones. Typical ring-opening catalysts are subject to unavoidable racemization of most OCA monomers, which hampers the synthesis of highly isotactic crystalline polymers. Here, we describe an effective bifunctional single-molecule organocatalysis for selective ring-opening polymerization of OCAs without epimerization. The close vicinity of both activating groups in the same molecule engenders an amplified synergetic effect and thus allows for the use of mild bases, thereby leading to minimal epimerization for polymerization. Ring-opening polymerization of manOCA monomer (OCA from mandelic acid) mediated by the bifunctional single-molecule organocatalyst yields highly isotactic poly(mandelic acid) (PMA) with controlled molecular weights (up to 19.8 kg mol-1). Mixing of the two enantiomers of PMA generates the first example of a crystalline stereocomplex in this area, which displayed distinct Tm values around 150 °C. Remarkably, the bifunctional catalysts are moisture-stable, recyclable, and easy to use, allowing sustainable and scalable synthesis of a stereoregular functional polyester.
- Tao, Youhua,Li, Maosheng,Tao, Yue,Tang, Jiadong,Wang, Yanchao,Zhang, Xiaoyong,Wang, Xianhong
-
p. 281 - 289
(2019/01/04)
-
- Chiral-at-Iron Catalyst: Expanding the Chemical Space for Asymmetric Earth-Abundant Metal Catalysis
-
A new class of chiral iron catalysts is introduced that contains exclusively achiral ligands with the overall chirality being the result of a stereogenic iron center. Specifically, iron(II) is cis-coordinated to two N-(2-pyridyl)-substituted N-heterocycli
- Hong, Yubiao,Jarrige, Lucie,Harms, Klaus,Meggers, Eric
-
supporting information
p. 4569 - 4572
(2019/03/19)
-
- Enantioselective Synthesis of the C23–C33 Fragment of Aetheramide A and Its C32 Epimer
-
The key aetheramide A intermediate with the natural (R,R,R) configuration along with the one having the unnatural (R,S,R) configuration was synthesized. The synthesis of both stereoisomers was accomplished by Suzuki coupling of two advanced chiral building blocks: (R,R)- and (R,S)-vinylboronates and an (R)-iodoalkene. The former was prepared from (R)-mandelic acid, and the latter was prepared by enantioselective allylation of 3-iodoacrylaldehyde.
- Peňa?ka, Tibor,Koukal, Petr,Kotora, Martin
-
supporting information
p. 147 - 149
(2018/01/27)
-
- Investigation of mechanistic pathway for trimethyl borate mediated amidation of (R)-mandelic acid for the synthesisof mirabegron, an antimuscarinic agent
-
The present work describes investigation of mechanistic pathway for trimethyl borate mediated amidation of (R)-mandelic acid (3) with 4-nitophenylethylamine (2) to provide (R)-2-hydroxy-N-[2-(4-nitrophenyl)ethyl]-2-phenylacetamide (4) during mirabegron synthesis. Plausible reaction mechanism is proposed by isolating and elucidating the active a-hydroxy ester intermediate 16 from the reaction mass. Trimethyl borate mediated approach proved to be selective in providing 4 without disturbing a-hydroxyl group and stereochemistry of the chiral center, and is also a greener, more economic and production friendly over the reported methods. The developed approach is rapid and efficient for the preparation of 4 with an overall yield of 85-87% and around 99.0% purity by HPLC at scale.
- Deshmukh, Dattatray G.,Bangal, Mukund N.,Patekar, Mukunda R.,Medhane, Vijay J.,Mathad, Vijayavitthal Thippannachar
-
p. 239 - 245
(2018/03/29)
-
- Autoamplification-Enhanced Oxidative Kinetic Resolution of sec-Alcohols and Alkyl Mandelates, and its Kinetic Model
-
In this contribution, the new dynamic nonlinear effect in asymmetric catalysis is discussed, manifesting itself in the oxidative kinetic resolution (OKR) of racemic secondary benzylic alcohols and alkyl mandelates with H2O2 in the presence of chiral Mn-based catalyst, with the apparent selectivity factor (krel) of the resolution being nonconstant over the reaction course. Typically, the initial growth of krel is changed into decay at high conversions. In this contribution, we demonstrate the oxidative kinetic resolution of various substrates bearing sec-alcoholic moieties, with the krel varying in different manners with increasing substrate conversion. We also present the predictive kinetic model of OKR with participation of asymmetric autoamplification. The influence of substrate and catalyst structure, as well as solvents and additives, on the behavior of krel variation, is discussed.
- Talsi, Evgenii P.,Bryliakov, Konstantin P.
-
p. 2693 - 2699
(2018/06/26)
-
- Remarkably improved stability and enhanced activity of a: Burkholderia cepacia lipase by coating with a triazolium alkyl-PEG sulfate ionic liquid
-
Three types of triazolium cetyl-PEG10 sulfate ionic liquid were synthesized and their activation of Burkholderia cepacia lipase was investigated; both the reaction rate and enantioselectivity depended on the cationic part of the coating ILs and 1-butyl-3-methyl-1,2,3-triazolium cetyl-PEG10 sulfate (Tz1)-coated lipase PS, which is especially suitable for the transesterification of 1-(pyridin-2-yl)ethanol, 1-(pyridin-3-yl)ethanol, and 1-(pyridin-4-yl)ethanol, among 12 types of tested secondary alcohol. The most important result was obtained when these enzymes were stored in an IL ([N221MEM][Tf2N]) solvent: Tz1-PS showed an amazing stability and it exhibited an excellent activity after 2 years when the enzyme was stored in [N221MEM][Tf2N].
- Nishihara,Shiomi,Kadotani,Nokami,Itoh
-
supporting information
p. 5250 - 5256
(2017/11/09)
-
- Amidation of unactivated ester derivatives mediated by trifluoroethanol
-
A catalytic amidation protocol mediated by 2,2,2-trifluoroethanol has been developed, facilitating the condensation of unactivated esters and amines, furnishing both secondary and tertiary amides. The complete scope and limitations of the method are described, along with modified conditions for challenging substrates such as acyclic secondary amines and chiral esters with retention of chiral integrity.
- McPherson, Christopher G.,Caldwell, Nicola,Jamieson, Craig,Simpson, Iain,Watson, Allan J. B.
-
supporting information
p. 3507 - 3518
(2017/04/26)
-
- Chemoenzymatic Preparation of Enantiomerically Enriched (R)-(–)-Mandelic Acid Derivatives: Application in the Synthesis of the Active Agent Pemoline
-
The enantioselective resolution of several racemic derivatives of mandelic acid methyl ester catalyzed by lipases from Pseudomonas fluorescens (Amano AK) or Burkholderia cepacia (Amano PS-C II and Amano PS-IM) has been achieved. A gram-scale lipase-mediated kinetic resolution approach has been developed that allows the facile synthesis of the corresponding methyl (R)-(–)-mandelates with excellent enantiomeric excesses (up to >99 % ee) and reaction enantioselectivity (E values up to >200). The dopaminergic agent pemoline, used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy, was synthesized with 98 % ee in a straightforward route by condensing the prepared methyl (R)-(–)-mandelate with guanidine hydrochloride under basic conditions. The desired (R)-(+)-pemoline in optically pure form (>99 % ee) was obtained after two recrystallizations from ethanol. However, it was confirmed by chiral HPLC that optically active pemoline undergoes racemization in methanol solution.
- Potera?a, Marcin,Dranka, Maciej,Borowiecki, Pawe?
-
p. 2290 - 2304
(2017/05/01)
-
- A thermoregulated phase-separable chiral Pt nanocatalyst for recyclable asymmetric hydrogenation of α-ketoesters
-
The design and preparation of a chiral Pt nanocatalyst system possessing thermoregulated phase-separation property and its application in recyclable asymmetric hydrogenation of α-ketoesters are presented.
- Xue, Xiuru,Wang, Yanhua,Han, Fu-She
-
supporting information
p. 3346 - 3349
(2017/03/22)
-
- Catalytic Promiscuity of Ancestral Esterases and Hydroxynitrile Lyases
-
Catalytic promiscuity is a useful, but accidental, enzyme property, so finding catalytically promiscuous enzymes in nature is inefficient. Some ancestral enzymes were branch points in the evolution of new enzymes and are hypothesized to have been promiscuous. To test the hypothesis that ancestral enzymes were more promiscuous than their modern descendants, we reconstructed ancestral enzymes at four branch points in the divergence hydroxynitrile lyases (HNL's) from esterases ~100 million years ago. Both enzyme types are α/β-hydrolase-fold enzymes and have the same catalytic triad, but differ in reaction type and mechanism. Esterases catalyze hydrolysis via an acyl enzyme intermediate, while lyases catalyze an elimination without an intermediate. Screening ancestral enzymes and their modern descendants with six esterase substrates and six lyase substrates found higher catalytic promiscuity among the ancestral enzymes (P 0.01). Ancestral esterases were more likely to catalyze a lyase reaction than modern esterases, and the ancestral HNL was more likely to catalyze ester hydrolysis than modern HNL's. One ancestral enzyme (HNL1) along the path from esterase to hydroxynitrile lyases was especially promiscuous and catalyzed both hydrolysis and lyase reactions with many substrates. A broader screen tested mechanistically related reactions that were not selected for by evolution: decarboxylation, Michael addition, γ-lactam hydrolysis and 1,5-diketone hydrolysis. The ancestral enzymes were more promiscuous than their modern descendants (P = 0.04). Thus, these reconstructed ancestral enzymes are catalytically promiscuous, but HNL1 is especially so.
- Devamani, Titu,Rauwerdink, Alissa M.,Lunzer, Mark,Jones, Bryan J.,Mooney, Joanna L.,Tan, Maxilmilien Alaric O.,Zhang, Zhi-Jun,Xu, Jian-He,Dean, Antony M.,Kazlauskas, Romas J.
-
p. 1046 - 1056
(2016/02/05)
-
- Dual pathway for the asymmetric transfer hydrogenation of α-ketoimides to chiral α-hydroxy imides or chiral α-hydroxy esters
-
In an enantioselective reaction, we expect to obtain two types of chiral products through a controllable strategy in asymmetric catalysis. Herein, we develop Ru-catalysed asymmetric transfer hydrogenation of α-ketoimides to realise an enantioselective construction of chiral α-hydroxy imides or chiral α-hydroxy esters. The transformation of α-ketoimides catalysed by (S,S)-[RuCl(η6-mesitylene)diamine] can afford various chiral α-hydroxy imides with high yields and enantioselectivities, whereas that catalysed by (S,S)-[RuCl(η6-hexamethylbenzene)diamine] gives the desirable chiral α-hydroxy esters through a slight adjustment of the reaction conditions. The method described here is a controllable organic transformation with sodium formate as a hydrogen source under mild reaction conditions, and the benefit of this transformation is that various chiral α-hydroxy imides or α-hydroxy esters can be obtained selectively from α-ketoimides. Selective directive: An enantioselective transformation in the Ru-catalyzed asymmetric transfer hydrogenation of α-ketoimides to chiral α-hydroxy imides or α-hydroxy esters is developed. The transformation of α-ketoimides catalyzed by (S,S)-[RuCl(η6-mesitylene)diamine] can afford various chiral α-hydroxy imides with high yields and enantioselectivities, whereas that catalyzed by (S,S)-[RuCl(η6-hexamethylbenzene)diamine] give desirable chiral α-hydroxy esters through a slight adjustment of reaction conditions.
- Zhao, Qiankun,Zhao, Yuxi,Liao, Hang,Cheng, Tanyu,Liu, Guohua
-
p. 412 - 416
(2016/02/05)
-
- An asymmetric pericyclic cascade approach to 3-alkyl-3-aryloxindoles: Generality, applications and mechanistic investigations
-
The reaction of L-serine derived N-arylnitrones with alkylarylketenes generates asymmetric 3-alkyl-3-aryloxindoles in good to excellent yields (up to 93%) and excellent enantioselectivity (up to 98% ee) via a pericyclic cascade process. The optimization, scope and applications of this transformation are reported, alongside further synthetic and computational investigations. The preparation of the enantiomer of a Roche anti-cancer agent (RO4999200) 1 (96% ee) in three steps demonstrates the potential utility of this methodology.
- Richmond, Edward,Ling, Kenneth B.,Duguet, Nicolas,Manton, Lois B.,elebi-?lcüm, Nihan,Lam, Yu-Hong,Alsancak, Sezen,Slawin, Alexandra M. Z.,Houk,Smith, Andrew D.
-
supporting information
p. 1807 - 1817
(2015/02/19)
-
- Chemo- And stereoselective reduction of β-keto-α-oximino nitriles by using baker's yeast
-
The baker's yeast mediated reduction of β-keto-α-oximino nitriles 3 at 20 ° C gave β-hydroxy-α-oximino nitriles 4 in high yields with high enantiomeric purity [enantiomeric excess (ee) values >99%]. At room temperature, the same reaction afforded the product in a slightly lower yield. The β-hydroxy-α-oximino nitriles 4 were obtained as single stereoisomers according to chiral GC-MS analyses and the 1H and 19F NMR spectra of the corresponding Mosher esters. The abso-lute stereochemistry of alcohol 4a was determined by hydrolysis of its oximino nitrile group followed by conversion into its corresponding α-hydroxy ester. The β-hydroxy-α-oximino nitrile products were further submitted to oxime- and nitrileselective transformations. This chemo- and stereoselective reduction can be used to generate important chiral building blocks.
- Mo, Kilwoong,Kang, Soon Bang,Kim, Youseung,Lee, Yong Sup,Lee, Jae Wook,Keum, Gyochang
-
p. 1137 - 1143
(2015/02/19)
-
- Identification of an ε-keto ester reductase for the efficient synthesis of an (R)-α-lipoic acid precursor
-
Abstract A novel reductase (CpAR2) with unusually high activity toward an ε-keto ester, ethyl 8-chloro-6-oxooctanoate, was isolated from Candida parapsilosis. The asymmetric reduction of ethyl 8-chloro-6-oxooctanoate using Escherichia coli cells coexpressing CpAR2 and glucose dehydrogenase genes gave ethyl (R)-8-chloro-6-hydroxyoctanoate, a key precursor for the synthesis of (R)-α-lipoic acid, in high space-time yield (530 gL-1d-1) and with excellent enantiomeric excess (>99%). This bioprocess was shown to be viable on a 10-L scale. This method provides a greener and more cost-effective method for the industrial production of (R)-α-lipoic acid.
- Zhang, Yu-Jun,Zhang, Wen-Xia,Zheng, Gao-Wei,Xu, Jian-He
-
supporting information
p. 1697 - 1702
(2015/06/02)
-
- Kinetic resolution of mandelate esters via stereoselective acylation catalyzed by lipase PS-30
-
By using lipase PS-30 as catalyst, the kinetic resolution of a series of racemic mandelate esters has been achieved via stereoselective acylation. The value of kinetic enantiomeric ratio (E) reached up to 197.5. Substituent effect is briefly discussed.
- Chen, Peiran,Yang, Wenhong
-
supporting information
p. 2290 - 2294
(2014/04/17)
-
- A chemoselective oxidation of monosubstituted ethylene glycol: Facile synthesis of optically active α-hydroxy acids
-
A mild and efficient method for the synthesis of optically active α-hydroxy acids through chemoselective oxidation of monosubstituted ethylene glycols using the TEMPO-NaOCl reagent system is described. It is evident from our studies that the solvent, pH and reaction temperature are very crucial for the success of this oxidation. The versatility of this method has been demonstrated with a variety of aliphatic, aromatic and carbohydrate substrates bearing various functional groups. the Partner Organisations 2014.
- Chinthapally, Kiran,Baskaran, Sundarababu
-
p. 4305 - 4309
(2014/06/23)
-
- Chirality switching in optical resolution of mandelic acid in C1-C4 alcohols: Elucidation of solvent effects based on x-ray crystal structures of diastereomeric salts
-
Chirality switching in the optical resolution of mandelic acid (MA) using (1R,2S)-2-amino-1,2-diphenylethanol (ADPE) in C1-C4 alcohols is demonstrated herein. Recrystallization of the diastereomeric mixture of the MA salts from longer alcohol solvents (n-PrOH, s-BuOH, i-BuOH, and n-BuOH) produced the (R)-MA salt, whereas the (S)-MA salt was preferentially deposited from shorter alcohol solvents (MeOH, EtOH, i-PrOH, and t-BuOH). Thermogravimetric analysis and 1H NMR spectroscopy showed that all the solvents employed were incorporated in the diastereomeric salts and the stability of the incorporated alcohols increased with an increase in the effective surface area of their alkyl chains. The X-ray crystal structures of the eight solvated diastereomeric salt pairs revealed that the type of hydrogen-bonding network (sheetlike or columnar) and the arrangement of the columnar structures were controlled by the length of the included alcohol. By comparison of the two diastereomeric MA salt crystal structures, their relative stability to display chirality switching was investigated.
- Kodama, Koichi,Shitara, Hiroaki,Hirose, Takuji
-
p. 3549 - 3556
(2014/07/21)
-
- Enantioselective palladium-catalyzed insertion of α-aryl-α- diazoacetates into the O-H bonds of phenols
-
A palladium-catalyzed asymmetric O-H insertion reaction was developed. Palladium complexes with chiral spiro bisoxazoline ligands promoted the insertion of α-aryl-α-diazoacetates into the O-H bond of phenols with high yield and excellent enantioselectivity under mild reaction conditions. This palladium-catalyzed asymmetric O-H insertion reaction provided an efficient and highly enantioselective method for the preparation of synthetically useful optically active α-aryl-α-aryloxyacetates.
- Xie, Xiu-Lan,Zhu, Shou-Fei,Guo, Jun-Xia,Cai, Yan,Zhou, Qi-Lin
-
supporting information
p. 2978 - 2981
(2014/04/03)
-
- Altering the substrate specificity of reductase CgKR1 from Candida glabrata by protein engineering for bioreduction of aromatic α-keto esters
-
A versatile keto ester reductase CgKR1, exhibiting a broad substrate spectrum, was obtained from Candida glabrata by genome data mining. It showed the highest activity toward an aliphatic β-keto ester, ethyl 4-chloro-3-oxobutanoate (COBE), but much lower activity toward bulkier α-keto esters with an aromatic group, such as methyl ortho- chlorobenzoylformate (CBFM) and ethyl 2-oxo-4-phenylbutyrate (OPBE). By rational design of the active pocket, the substrate specificity of the reductase was significantly altered and this tailor-made reductase showed a much higher activity toward aromatic α-keto esters (~7-fold increase in k cat/Km toward CBFM) and lower activity toward aliphatic keto esters (~12-fold decrease in kcat/Km toward COBE). Meanwhile, the thermostability of the reductase was enhanced by a consensus approach. Such improvements may yield practical catalysts for the asymmetric bioreduction of these aromatic α-keto esters
- Huang, Lei,Ma, Hong-Min,Yu, Hui-Lei,Xu, Jian-He
-
p. 1943 - 1948
(2014/07/07)
-
- Preparation of bonded cellulose tris(3,5-dimethylphenylcarbamate) chiral stationary phases by using three bifunctional reagents
-
Three di-acyl chlolide reagents, adipoyl chloride, terephthaloyl chloride and isophthaloyl chloride, were used as spacer reagents to prepare bonded type of three cellulose (3,5-dimethylphenyl)carbamate (CDMPC) chiral stationary phases (CSPs). The CDMPC CSPs were prepared using these three acid chlorides as spacer agents at the 6-position of the primary hydroxyl group on the glucose unit of cellulose regioselectively. The chiral recognition ability of the prepared CSPs for five racemates was evaluated by normal-phase high-performance liquid chromatography (HPLC) with the following mobile phases: hexane/isopropanol (IPA), hexane/IPA/ tetrahydrofuran (THF) and hexane/IPA/chloroform. The result showed that these prepared CSPs can be used in THF and chloroform solutions and the chiral recognition abilities of the CSPs were improved depending on the eluents and chiral samples.
- Zhang, Yi Jun,Huang, Mingxian,Zhang, Yuping,Ryoo, Jae Jeong
-
p. 2623 - 2628
(2013/10/22)
-
- Cyclodextrin-based ionic liquids as enantioselective stationary phases in gas chromatography
-
New permethylated mono-6-deoxy-6-pyridin-1-ium and mono-6-deoxy-6-(1-vinyl- 1H-imidazol-3-ium)-α- and -β-cyclodextrin trifluoromethanesulfonate ionic liquids were synthesized from the corresponding permethylated mono-6-hydroxycyclodextrins in a one-pot reaction and solvent-free procedure. Regioselective transformation of native α- and β-cyclodextrins with the use of a bulky tert-butyldiphenylsilyl protecting group afforded the desired 6-monosubstituted permethylated cyclodextrin derivatives in moderate yields. The new ionic liquids were tested as stationary phases in capillary GC columns towards chiral discrimination in enantio-GC analysis of racemic mixtures. The permethylated 6-deoxy-6-pyridin-1-ium-α-cyclodextrin trifluoromethanesulfonate displayed good enantiomeric separations for some racemic esters and lactones, as well as epoxides. In particular, for both the racemic whiskey lactone and the high boiling point menthyl laurate, not successfully separated in a commercial cyclodextrin phase, the enantiomeric separations were achieved isothermally at 140 °C. In phase: Permethylated mono-6-hydroxy-α- and -β-cyclodextrins react with pyridine or 1-vinylimidazole in the presence of triflic anhydride in a solvent-free procedure to yield new roomerature ionic liquids (ILs). These ILs have been used as stationary phases in gas chromatography; enantiomeric separations are achieved (see figure for whiskey lactone) with permethylated mono-6-deoxy-6-(pyridin-1-ium)-α-cyclodextrin trifluoromethanesulfonate. Copyright
- Costa, Nuno,Matos, Sara,Da Silva, Marco D. R. Gomes,Pereira, M. Manuela A.
-
p. 1466 - 1474
(2014/01/06)
-
- Chemoselective esterification of α-hydroxyacids catalyzed by salicylaldehyde through induced intramolecularity
-
A new, direct and chemoselective esterification of α-hydroxyacids was developed using a reversible covalent-binding strategy. By taking advantage of acetal chemistry, simple aldehydes can be used to efficiently catalyze the esterification of α-hydroxy carboxylic acids in the presence of β-hydroxyacid moieties or other carboxylic acids in amounts equal to or in excess of the alcohols. A diverse array of α-aryl, α-alkyl, α-heteroaryl, and functionalized α-hydroxyacids were smoothly esterified with 1° and 2° alcohols catalyzed by 10 mol% inexpensive and commercially available salicylaldehyde, furnishing the resultant esterification products in 83-95% yields after a simple basic aqueous workup to remove the unreacted hydroxyacids. In addition, the salicylaldehyde can be recovered through vacuum distillation or silica gel purification, thereby meeting the standards of green chemistry. A mechanistic study proved that the formation of covalent adduct III during our proposed catalytic cycle (Scheme 1A) is responsible for the real catalysis.
- Weng, Shiue-Shien,Li, Hsin-Chun,Yang, Teng-Mao
-
p. 1976 - 1986
(2013/03/13)
-
- Diametric stereocontrol in dynamic catalytic reduction of racemic acyl phosphonates: Divergence from α-Keto ester congeners
-
An unexpected dichotomy was observed in the Ru-catalyzed asymmetric transfer hydrogenation of acyl phosphonates: reduction proceeded from the opposite face relative to that observed in the analogous reduction of α-keto esters. The first highly selective catalytic hydrogenation of acyl phosphonates was utilized in the dynamic kinetic resolution of α-aryl acyl phosphonates, providing β-stereogenic α-hydroxy phosphonic acid derivatives.
- Corbett, Michael T.,Johnson, Jeffrey S.
-
supporting information
p. 594 - 597
(2013/03/13)
-
- A homochiral porous metal-organic framework for enantioselective adsorption of mandelates and photocyclizaton of tropolone ethers
-
A chiral porous metal-organic framework of an axially C2- symmetric 1,1′-biphenol ligand is constructed and can be used as a solid-state host to enanioselectively adsorb mandelates with up to 93.1% ee and to entrap achiral tropolone ethers and
- Peng, Yongwu,Gong, Tengfei,Cui, Yong
-
supporting information
p. 8253 - 8255
(2013/09/12)
-
- Solution-phase synthesis and evaluation of tetraproline chiral stationary phases
-
A protocol was developed for the solution-phase synthesis of multigram amounts of two 9-fluorenylmethoxycarbonyl (Fmoc)-protected tetraproline peptides. These tetraproline peptides were then attached to amino derivatized silica gel. The replacement of the Fmoc group with the trimethylacetyl group lead to two tetraproline chiral stationary phases (CSPs). A comparison of the chromatographic behavior of these two solution-phase-synthesized tetraproline CSPs with that prepared by stepwise solid-phase synthesis revealed that all three had similar chromatographic performance for resolving 53 model analytes. This suggests that the solution-phase synthesis of oligoprolines, which allows for the specific benefits of good batch reproducibility, selector homogeneity, and possibly low cost, is a feasible alternative to the solid-phase synthesis of oligoproline CSPs. Copyright
- Dai, Zhi,Ye, Guozhong,Pittman Jr., Charles U.,Li, Tingyu
-
experimental part
p. 329 - 338
(2012/05/20)
-
- Enantioseparation of typical pesticides using cellulose carbamate stationary phases by capillary liquid chromatography
-
Cellulose-tris(3,5-dimethylphenylcarbamate) was initially synthesized as the chiral selector, then stable coated and bonded chiral stationary phases were prepared, respectively, using aminopropyl-functionalized silica gel as the support media. The prepared stationary phases were used for micro-column chiral separation by self-installed capillary high performance liquid chromatography system. Eighteen kind of chiral compounds including some typical pesticides were tested on both prepared chiral stationary phases and different chromatographic parameters such as resolution and retention time were comparatively investigated.
- Bai, Lian-Yang,Zhang, Yu-Ping,Deng, Pu-Hong,Zhang, Yi-Jun,Chen, Jun
-
experimental part
p. 4917 - 4922
(2012/10/08)
-
- Heterogeneous enantioselective hydrogenation in a continuousflow fixed-bed reactor system: Hydrogenation of activated ketones and their binary mixtures on pt-alumina-cinchona alkaloid catalysts
-
Under the experimental conditions of the Orito reaction the individual hydrogenation and the competitive hydrogenations of three binary mixtures of methyl benzoylformate (MBF), pyruvic aldehyde dimethyl acetal (PA) and 2,2-diethoxyacetophenone (DAP) on platinum-alumina catalysts modified by cinchonidine, cinchonine, quinine and quinidine (Pt-CD, Pt-CN, Pt-QN, Pt-QD) were studied for the first time using continuous-flow fixed-bed reactor system. Conversions of chiral (Cc) and racemic (Cr) hydrogenations of all three compounds and enantioselectivities (ee) were determined under the same experimental conditions (under 4 MPa H2 pressure, at room temperature using toluene/AcOH 9/1 as solvent).The order of the rates of the enantioselective hydrogenations of the three substrates studied is MBF > PA > DAP, and the order of their ee values is MBF ? PA > DAP. The hydrogenation rate and the effect of rate on ee depend on the structure of the cinchona used: hydrogenation of MBF and PA may produce ee values over 90 %, however, the ee values were conspicuously low in the presence of Pt-QN and especially of Pt-QD catalysts. In the chiral hydrogenation of DAP considering racemic hydrogenation rate decrease (Cc/Cr 1) takes place instead of rate enhancement over all four catalysts. The new experimental data supported the so far known fundamental rules of the Orito reaction based on batch studies. Springer Science+Business Media, LLC 2012.
- Sz?ll?si, Gyo?rgy,Makra, Zsolt,Fekete, Mónika,Fül?p, Ferenc,Bartók, Mihály
-
experimental part
p. 889 - 894
(2012/10/18)
-
- Efficient synthesis of a chiral precursor for angiotensin-converting enzyme (ace) inhibitors in high space-time yield by a new reductase without external cofactors
-
A new reductase, CgKR2, with the ability to reduce ethyl 2-oxo-4-phenylbutyrate (OPBE) to ethyl (R)-2-hydroxy-4-phenylbutyrate ((R)-HPBE), an important chiral precursor for angiotensin-converting enzyme (ACE) inhibitors, was discovered. For the first time, (R)-HPBE with >99% ee was produced via bioreduction of OPBE at 1 M without external addition of cofactors. The space-time yield (700 g·L-1·d -1) was 27 times higher than the highest record.
- Shen, Nai-Dong,Ni, Yan,Ma, Hong-Min,Wang, Li-Juan,Li, Chun-Xiu,Zheng, Gao-Wei,Zhang, Jie,Xu, Jian-He
-
supporting information; experimental part
p. 1982 - 1985
(2012/06/01)
-
- Fundamental insights into the enantioselectivity of hydrogenations on cinchona-modified platinum and palladium
-
The influence of the configuration at the C8 and C9 positions of cinchona alkaloids was investigated by comparing the efficiency of cinchonidine, cinchonine, and 9-epi-cinchonidine as chiral modifiers. In the hydrogenation of ketones (methyl benzoylformate, ketopantolactone, methylglyoxal dimethylacetal, 2,2,2-trifluoroacetophenone) on Pt, a change in the configuration at C9 did not affect the absolute configuration of the main products; however, the ees and rates dropped significantly. In the hydrogenation of α-functionalized olefins (E-2-methyl-2-hexenoic acid, 2-phenylcinnamic acid, and 4-methoxy-6-methyl-2H-pyran-2-one) on Pd, replacement of cinchonidine or cinchonine by epi-cinchonidine diminished the rates and almost eliminated the enantioselection, indicating that a subtle combination of C8 and C9 configurations is required on Pd. DFT calculations of the adsorption of the modifiers and the nonlinear behavior of modifier mixtures revealed that the lower reaction rates observed for 9-epi-cinchonidine-modified surfaces cannot be related to different adsorption strength of this modifier. Additionally, substrate-modifier docking interactions are presented.
- Schmidt, Erik,Bucher, Christoph,Santarossa, Gianluca,Mallat, Tamas,Gilmour, Ryan,Baiker, Alfons
-
experimental part
p. 238 - 248
(2012/06/01)
-
- Stereospecific reduction of methyl o-chlorobenzoylformate at 300 g·L-1 without additional cofactor using a carbonyl reductase mined from Candida glabrata
-
In order to search for oxidoreductases suitable for the preparation of methyl (R)-o-chloromandelate [(R)-CMM], the key intermediate for clopidogrel, the homologous proteins of Gre2p were expressed in Escherichia coli, among which CgKR1 showed the most satisfactory activity and stereoselectivity towards methyl o-chlorobenzoylformate (CBFM). Using the crude enzyme of CgKR1 and glucose dehydrogenase (GDH), as much as 300 g·L-1 of CBFM was almost stoichiometrically converted to (R)-CMM with excellent enantiomeric excess (98.7% ee). More importantly, the reaction could be performed without external addition of an expensive cofactor. The substrate profile indicates that keto esters serve as the most suitable substrate, which was confirmed by gram-scale preparations. Homology modeling and docking analysis revealed the molecular basis for the high stereoselectivity of CgKR1. These demonstrate not only the feasibility of in silico mining of novel enzymes based on sequence homology but also the applicability of this new reductase for the practical production of optically active (R)-CMM. Copyright
- Ma, Hongmin,Yang, Linlin,Ni, Yan,Zhang, Jie,Li, Chun-Xiu,Zheng, Gao-Wei,Yang, Huaiyu,Xu, Jian-He
-
experimental part
p. 1765 - 1772
(2012/08/08)
-
- New phenomenon in competitive hydrogenation of binary mixtures of activated ketones over unmodified and cinchonidine-modified Pt/alumina catalyst
-
Competitive hydrogenations of eight binary mixtures of ethyl pyruvate (EP), methyl benzoylformate (MBF), ketopantolactone (KPL), pyruvic aldehyde dimethyl acetal (PA) and trifluoroacetophenone (TFAP) on platinum/alumina catalysts unmodified (racemic hydrogenation) and modified by cinchonidine (chiral hydrogenation) were studied under the experimental conditions of the Orito reaction. Reaction rates of chiral and racemic hydrogenations were determined and relative adsorption coefficients were calculated. In the competitive chiral hydrogenation of EP + MBF, EP + TFAP and KPL + MBF binary mixtures a new phenomenon was observed: namely the EP and KPL are hydrogenated faster than MBF and TFAP, whereas in racemic one the MBF and TFAP are hydrogenated faster than EP or KPL. Effects of the activated ketones structure on their reactivity and the stability of the surface complexes are discussed. It was found that differences in rate enhancement are caused by the differences both in the adsorptivity and in the reactivity of adsorbed substrates and adsorbed intermediate complexes.
- Balázsik, Katalin,Szori, Kornél,Szollosi, Gy?rgy,Bartók, Mihály
-
experimental part
p. 1410 - 1414
(2012/07/31)
-
- Hydrogenation of acetophenone derivatives: Tuning the enantioselectivity via the metal-support interaction
-
The influence of acidic and basic supports on the enantioselective hydrogenation of acetophenone and its aryl-substituted derivates was studied. The Pt/Al2O3, Pt/Al2O3-SiO 2, and Pt/Al2O3-Cs2O catalysts were prepared by single-step flame spray pyrolysis, and cinchonidine (CD) was used as chiral modifier. For all five aromatic ketones, the acidic support improved the ee, while the basic support diminished it. Opposite tendencies were observed for the reaction rate: acidic support lowered and basic support enhanced the rate of ketone conversion. In situ investigation of the hydrogenation of the quinoline ring of CD revealed for the first time that degradation of the modifier leads to remarkable variation in the substrate/modifier ratio. This effect and a possible catalyst deactivation due to aldol condensation of the ketones may be the origin of the decrease in ee with conversion. Following the diastereoselectivity during hydrogenation of the heteroaromatic ring of the quinoline unit of CD proved dominantly pro(S) adsorption mode on Pt/Al 2O3 and Pt/Al2O3-SiO2, and pro(R) on Pt/Al2O3-Cs2O catalysts. Changes in the adsorption mode were minor during hydrogenation of aromatic ketones. This, together with the small effect of ketones on the hydrogenation rate of CD, is interpreted as an indication to weak substrate-modifier interactions, in contrast to the situation during the hydrogenation of α-ketoesters (methyl benzoylformate).
- Hoxha, Fatos,Schmidt, Erik,Mallat, Tamas,Schimmoeller, Bjoern,Pratsinis, Sotiris E.,Baiker, Alfons
-
scheme or table
p. 94 - 101
(2011/04/26)
-
- The first case of competitive heterogeneously catalyzed hydrogenation using continuous-flow fixed-bed reactor system: Hydrogenation of binary mixtures of activated ketones on Pt-alumina and on Pt-alumina-cinchonidine catalysts
-
Under the experimental conditions of the Orito reaction the competitive hydrogenations of four binary mixtures of ethyl pyruvate (EP), methyl benzoylformate (MBF), pyruvic aldehyde dimethyl acetal (PA) and 2,2-diethoxyacetophenone (DAP) on unmodified Pt/Al2O3 (racemic hydrogenation) and catalyst modified by cinchonidine (chiral hydrogenation) were studied using continuous-flow fixed-bed reactor system (CFBR). Conversions of chiral and racemic hydrogenations were determined under 4 MPa H2 pressure, at 293 K using toluene/acetic acid 9/1 as solvent. In the competitive chiral hydrogenation of MBF + EP and DAP + PA binary mixtures (S1 + S2) a new phenomenon was observed: namely the EP and PA are hydrogenated faster than MBF and DAP, whereas in racemic one the MBF and DAP are hydrogenated faster than the former ketones. The phenomenon verified for the first time in CFBR is dependent on the adsorption mode of the surface complexes of various compositions (S1-Pt, S2-Pt, S1-CD-Pt, S2-CD-Pt, CD = cinchonidine). In the chiral hydrogenation of DAP a rate decrease, i.e., "ligand deceleration" was observed instead of rate enhancement. Graphical Abstract: [Figure not available: see fulltext.]
- Sz?ll?si, Gyo?rgy,Makra, Zsolt,Fül?p, Ferenc,Bartók, Mihály
-
scheme or table
p. 1616 - 1620
(2012/03/08)
-
- Asymmetric aerobic oxidation of α-hydroxy acid derivatives catalyzed by reusable, polystyrene-supported chiral N-salicylidene oxidovanadium tert-leucinates
-
The direct immobilization of two different C-5-propargyl ether-modified, chiral N-salicylidene vanadyl(V) tert-leucinates onto 4-azidomethyl-substituted polystyrene by click chemistry was examined. Among the eight different solvents investigated, the resulting polystyrene-supported catalysts promote the asymmetric, aerobic oxidation of α-hydroxy (thio)esters and amides with enantioselectivities of up to 99% ee (selectivity factor up to 41) in chloroform. These polystyrene-supported catalysts can be readily recovered by filtration and reused for at least four consecutive runs without discernible loss of reactivity and enantioselectivity.
- Salunke, Santosh B.,Babu, N.Seshu,Chen, Chien-Tien
-
p. 1234 - 1240
(2011/06/26)
-
- 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)
-
- Stereomodulating effect of remote groups on the NADH-mimetic reduction of alkyl aroylformates with 1,4-dihydronicotinamide-β-lactam amides
-
Conformationally restricted NADH peptidomimetics 4a-e, characterized by the presence of a (1,4-dihydronicotinamide)-(β-lactam) moiety, have been synthesized and used to study the Mg2+ cation-promoted asymmetric reduction of alkyl aroylformates
- Aizpurua, Jesus M.,Palomo, Claudio,Fratila, Raluca M.,Ferrón, Pablo,Miranda, José I.
-
supporting information; experimental part
p. 3187 - 3194
(2010/06/12)
-
- First total synthesis of (+)-crassalactone A
-
A simple and highly efficient first total synthesis of cytotoxic (+)-crassalactone A starting from (R)-mandelic acid is described. The strategy involves the osmium tetroxide-catalyzed cis-hydroxylation and the stereoselective addition of ethyl lithiopropi
- Shekhar,Kumar Reddy,Suresh,Chanti Babu,Venkateswarlu
-
scheme or table
p. 946 - 948
(2010/04/29)
-
- Enantioselective iron-catalysed O-H bond insertions
-
The ready availability, low price and environmentally benign character of iron mean that it is an ideal alternative to precious metals in catalysis. Recent growth in the number of iron-catalysed reactions reported reflects an increasing demand for sustainable chemistry. Only a limited number of chiral iron catalysts have been reported and these have, in general, proven less enantioselective than other transition-metal catalysts, thus limiting their appeal. Here, we report that iron complexes of spiro-bisoxazoline ligands are highly efficient catalysts for asymmetric O-H bond insertion reactions. These complexes catalyse insertions into the O-H bond of a wide variety of alcohols and even water, with exceptional enantioselectivities under mild reaction conditions. The selectivities surpass those obtained with other transition-metal catalysts. This study should inspire and encourage the use of iron instead of traditional precious metals in the development of greener catalysts for catalytic asymmetric synthesis.
- Zhu, Shou-Fei,Cai, Yan,Mao, Hong-Xiang,Xie, Jian-Hua,Zhou, Qi-Lin
-
experimental part
p. 546 - 551
(2010/10/04)
-
- Chiral induction by Cinchona alkaloids in the rhodium(II) catalyzed O-H insertion reaction
-
Cinchona alkaloids are effective additives for enantioselective O-H insertion of α-phenyldiazoacetate and water by rhodium(II) complexes. Addition of silica gel promotes O-H insertion in the reaction rate and the reaction proceeds smoothly at less than the freezing point of water, e.g., -10°C, and provided mandelate in up to 50% ee. The results reported here are the highest asymmetric inductions obtained to date for O-H insertions via a Rh-carbenoid.
- Saito, Hiroaki,Iwai, Ryo,Uchiyama, Taketo,Miyake, Muneharu,Miyairi, Shinichi
-
experimental part
p. 872 - 874
(2010/09/04)
-