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The effect of the reaction parameters water activity and reaction solvent was investigated for the dynamic kinetic resolution (DKR) of rac -benzoin with immobilized Lipase TL as biocatalyst for transesterification and the heterogeneous chemo-catalyst Zr-TUD-1 (Si/Zr = 25) for in situ racemization. Overall dry reaction conditions led to the best results for both catalysts. The immobilized lipase in a more environmentally benign solvent like cyclopentyl methyl ether (CPME) exhibited a 1.6-fold higher activity and an up to 1.5-fold higher half-life time than in the standard solvents such as toluene and 2-methyltetrahydrofuran (2-MeTHF). Among a variety of deep eutectic solvents (DESs) choline chloride:isosorbide (ChCl:Iso) was found to be suitable for the reaction system. The activity was lower than in the aforementioned solvents, but the very low solubility of the product ( S )-benzoin butyrate in ChCl:Iso compared to the investigated organic solvents possesses great potential with respect to downstream processing. Optimized reaction parameters (dry CPME) were applied for DKR in batch and continuous mode yielding comparable or slightly better results than in toluene or 2-MeTHF. [ABSTRACT FROM AUTHOR]

The ubiquitous structure of δ-lactones makes the development of new methods for their enantioselective and stereoselective synthesis an important ongoing challenge. The intermolecular dynamic kinetic resolution (DKR) of β-halo-α-ketoesters cooperatively catalyzed by an N-heterocyclic carbene and a Lewis acid generates two contiguous stereocenters with remarkable diastereoselectivity through an oxidation/ lactonization sequence. [ABSTRACT FROM AUTHOR]

The ubiquitous structure of δ-lactones makes the development of new methods for their enantioselective and stereoselective synthesis an important ongoing challenge. The intermolecular dynamic kinetic resolution (DKR) of β-halo-α-ketoesters cooperatively catalyzed by an N-heterocyclic carbene and a Lewis acid generates two contiguous stereocenters with remarkable diastereoselectivity through an oxidation/lactonization sequence. [ABSTRACT FROM AUTHOR]

A family of ruthenium complexes with different ligands was utilized in racemization of ( R )-1-phenylethanol to investigate the potential influence of the ligands coordinated to the ruthenium center. Kinetic experiments showed that 16-electron cymene ruthenium complex with two chloro-bridge bonds and 18-electron ones with easily dissociative ligands are highly active for catalytic racemization of alcohols. Possible racemization mechanism for cymene ruthenium complexes was then proposed. Computational analysis of dissociation energy barrier, NBO analysis and reaction potential energy surface suggest that ligand-dissociation process is the vital step of the racemization catalyzed by cymene ruthenium complexes. Thereafter, these complexes were applied in the DKR of secondary alcohols to verify their efficiency and applicability. [ABSTRACT FROM AUTHOR]

A mild and robust direct CH functionalization strategy has been applied to the synthesis of axially chiral biaryls. Such an efficient and stereoselective transformation occurs through an original dynamic kinetic resolution pathway enabling the conversion of diastereomeric mixtures of non-prefunctionalized substrates into atropisomerically pure, highly substituted biaryl scaffolds. The main feature of this transformation is the use of an enantiopure sulfoxide as both chiral auxiliary and traceless directing group. The potential of newly synthesized biaryls as valuable building blocks is further illustrated. [ABSTRACT FROM AUTHOR]

A convenient and efficient route has been successfully developed for preparing (4a R ,7a S )-6-benzyltetrahydro-1H-pyrrolo[3,4-b]pyridine-5,7(6H,7aH)-dione through enzyme-mediated kinetic resolution processes under mild and environmentally acceptable conditions. Different reaction condition factors, including acyl agent, solvent, reaction temperature, and the concentration of Et 3 N, were optimized in order to establish the optimal reaction conditions for the enzymatic kinetic resolution of secondary amines. It was demonstrated that acyl agent, the concentration of Et 3 N or the type of solvent have a greater influence on the selectivity and rate of the asymmetric acylation reaction in the process of the enzymatic resolution, respectively. The target product amine was obtained in good conversion (49%) and an excellent degree of enantiomeric purity (>99%) when Candida antarctica lipase B (CAL-B) and phenyl allyl carbonates were combined to use in the tert-butyl methyl ether (TBME) medium. This method will be an alternative to the traditional route for producing the optically pure intermediate of moxifloxacin. [ABSTRACT FROM AUTHOR]

A synthetic protocol making use of a well-defined cationic ruthenium complex 2 enabling the racemization of enantiomerically pure secondary alcohols in the presence of a weak base (K2CO3) is described. The compatibility of 2 with Candida Antarctica lipase B (Novozym 435) allows the development of an efficient dynamic kinetic resolution of sec-alcohols in the absence of an additional strong base. This procedure involves the first example of a dynamic kinetic resolution of alcohols in the presence of a cationic ruthenium catalyst. In addition, we describe the conversion of ketones to the enantioenriched acetates in a one-pot reaction, probing the versatility of complex 2. [ABSTRACT FROM AUTHOR]

Strategies on the construction of enantiomerically pure silicon-stereogenic silanes generally relies on desymmetrization of prochiral and symmetric substrates. However, dynamic kinetic asymmetric transformations of organosilicon compounds have remained underdeveloped and unforeseen owing to a lack of an effective method for deracemization of the static silicon stereocenters. Here we report the first Rh-catalyzed dynamic kinetic asymmetric intramolecular hydrosilylation (DyKAH) with "silicon-centered" racemic hydrosilanes that enables the facile preparation of silicon-stereogenic benzosiloles in good yields and excellent enantioselectivities. The special rhodium catalyst controlled by non-diastereopure-type mixed phosphine-phosphoramidite ligand with axial chirality and multiple stereocenters can induce enantioselectivity efficiently in this novel DyKAH reaction. Density functional theory (DFT) calculations suggest that the amide moiety in chiral ligand plays important role in facilitating the S N 2 substitution of chloride ion to realize the chiral inversion of silicon center., (© 2022 Wiley-VCH GmbH.)

Natural lipases typically recognize enantiomers of alcohols based on the size differences of substituents near the carbinol moiety and selectively react with the R enantiomers of secondary alcohols. Therefore, lipase-catalyzed dynamic kinetic resolution (DKR) of racemic secondary alcohols produces only R enantiomers. We report herein a method for obtaining S enantiomers by DKR of secondary 3-(trialkylsilyl)propargyl alcohols by using a well-known R-selective Pseudomonas fluorescens lipase in combination with a racemization catalyst VMPS4, in which the silyl group reverses the size relationship of substituents near the carbinol moiety. We have already reported R-selective DKR of the corresponding propargyl alcohols without substituents on the ethynyl terminal carbon, and the presence of an easily removable silyl group has enabled us to produce both enantiomers of propargyl alcohols in high chemical yields and with high enantiomeric excess. In addition, immobilization of the lipase on Celite was found to be important for achieving a high efficiency of the DKR., (© 2022 Wiley-VCH GmbH.)

Catalytic asymmetric dynamic kinetic resolution of configurationally labile bridged biaryls is emerging as a powerful strategy for atropisomer synthesis. However, the reported examples suffer from an inherent challenge as the reactivity is highly dependent on the torsional strain of the biaryl substrates, which significantly narrows down the scope and hampers the application. Herein, we report our discovery and development of a torsional strain-independent reaction between biaryl thionolactones and activated isocyanides. By employing auto-tandem silver catalysis, a universal synthesis of both tri- and tetra-ortho-substituted thiazole-containing biaryls was realized in high yields with high enantioselectivities. In addition, these products could be facilely converted to a novel type of bridged biaryls bearing an eight-membered lactone. Mechanistic studies were carried out to elucidate the cause of this unusual torsional strain-independent reactivity., (© 2022 Wiley-VCH GmbH.)

Chiral β‐hydroxysulfides are an important class of organic compounds which find broad application in organic and pharmaceutical chemistry. Herein we describe the development of novel biocatalytic and chemoenzymatic methods for the enantioselective synthesis of β‐hydroxysulfides by exploiting ketoreductase (KRED) enzymes. Four KREDs were discovered from a pool of 384 enzymes identified and isolated through a metagenomic approach. KRED311 and KRED349 catalysed the synthesis of β‐hydroxysulfides bearing a stereocentre at the C−O bond with opposite absolute configurations and excellent ee values by novel chemoenzymatic and biocatalytic‐chemical‐biocatalytic (bio‐chem‐bio) cascades starting from commercially available thiophenols/thiols and α‐haloketones/alcohols. KRED253 and KRED384 catalysed the enantioselective synthesis of β‐hydroxysulfides bearing a stereocentre at the C−S bond with opposite enantioselectivities by dynamic kinetic resolution (DKR) of racemic α‐thioaldehydes. [ABSTRACT FROM AUTHOR]

We herein report a catalyst system for the dynamic kinetic resolution of secondary alcohols by combining the enzymatic resolution with an iron-catalyzed racemization. A new air-stable tricarbonyl (cyclopentadienone)iron complex is identified as the active racemization catalyst for this transformation without any additive. Various substrates including benzylic, heteroaromatic, aliphatic alcohols can be used and afford the corresponding esters in good yields and with excellent enantioselectivities. [ABSTRACT FROM AUTHOR]

A highly efficient dynamic kinetic resolution system for secondary aromatic alcohol using low-cost sulfonated sepiolite as a racemization catalyst has been developed. The system operates at 25 °C, achieves good ee p (>99%) and substrate conversion ratio (>99%), is applicable to a variety of substrates and can be reused more than 10 times. [ABSTRACT FROM AUTHOR]

A chiral Lewis base organocatalyzed asymmetric hydrosilylation of α-substituted β-enamino esters is presented. The reactions proceeded through dynamic kinetic resolution to afford various enantioenriched β2-amino esters with high yields (up to 98%) in moderate enantioselectivities (up to 77% ee). [ABSTRACT FROM AUTHOR]

A bienzymatic system comprising an N -succinylamino acid racemase from Geobacillus kaustophilus CECT4264 (GkNSAAR) and an enantiospecific l - N -carbamoylase from Geobacillus stearothermophilus CECT43 (BsLcar) has been developed. This biocatalyst has been able to produce optically pure natural and non-natural l -amino acids starting from racemic mixtures of N -acetyl-, N -formyl- and N -carbamoyl-amino acids by dynamic kinetic resolution. The fastest conversion rate was found with N -formyl-amino acids, followed by N -carbamoyl- and N -acetyl-amino acids, and GkNSAAR proved to be the limiting step of the system due to its lower specific activity. Metal ion cobalt was essential for the activity of the biocatalyst and the system was optimally active when Co 2+ was added directly to the reaction mixture. The optimum pH for the biocatalyst proved to be 8.0, for both N -formyl- and N -carbamoyl-amino acid substrates, whereas optimum temperature ranges were 45–55 °C for N -formyl-amino acids and 55–70 °C for N -carbamoyl-derivatives. The bienzymatic system was equally efficient in converting aromatic and aliphatic substrates. Total conversion was also achieved using high substrate concentrations (100 and 500 mM) with no noticeable inhibition. This “Amidohydrolase Process” enables the production of both natural and non-natural l -amino acids from a broad substrate spectrum with yields of over 95%. [ABSTRACT FROM AUTHOR]

Abstract: The asymmetric synthesis of 1,3-oxathiolan-5-one derivatives through an enzyme-catalyzed, dynamic covalent kinetic resolution strategy is presented. Dynamic hemithioacetal formation combined with intramolecular, lipase-catalyzed lactonization resulted in good conversions with moderate to good enantiomeric excess (ee) for the final products. The process was evaluated for different lipase preparations, solvents, bases, and reaction temperatures, where lipase B from Candida antarctica (CAL-B) proved most efficient. The substrate scope was furthermore explored for a range of aldehyde structures, together with the potential access to nucleoside analog inhibitor core structures. [Copyright &y& Elsevier]

Abstract: In this study, a nitrilase-CLEA mediated dynamic kinetic resolution for the asymmetric synthesis of d-N-formyl-phenylglycine was developed. Cross-linked enzyme aggregates (CLEAs) of nitrilase from Sphingomonas wittichii RW1 were first prepared and characterized. Compared with the free nitrilase, nitrilase-CLEAs showed higher stability against various conditions such as pH and temperature. The nitrilase-CLEA catalyzed dynamic kinetic resolution of N-formyl-phenylglycinonitrile was further optimized. Under the optimal conditions, the yield and ee value of N-d-formyl-phenylglycine achieved 95% and 97%, respectively. Additionally, the nitrilase-CLEAs could be repeatedly used in the batch biotransformation, and the activity retained more than 70% of the initial activity after 6 batches. These results indicated that the nitrilase-CLEA mediated dynamic kinetic resolution was a promising method for the synthesis of d-N-formyl-phenylglycine. [Copyright &y& Elsevier]

This review describes our recent works on the diastereo- and enantioselective synthesis of anti-β-hydroxy-α-amino acid esters using transition-metal-chiral-bisphosphine catalysts. A variety of transition metals, namely ruthenium ( Ru), rhodium ( Rh), iridium ( Ir), and nickel ( Ni), in combination with chiral bisphosphines, worked well as catalysts for the direct anti-selective asymmetric hydrogenation of α-amino-β-keto ester hydrochlorides, yielding anti-β-hydroxy-α-amino acid esters via dynamic kinetic resolution ( DKR) in excellent yields and diastereo- and enantioselectivities. The Ru-catalyzed asymmetric hydrogenation of α-amino-β-ketoesters via DKR is the first example of generating anti-β-hydroxy-α-amino acids. Complexes of iridium and axially chiral bisphosphines catalyze an efficient asymmetric hydrogenation of α-amino-β-keto ester hydrochlorides via dynamic kinetic resolution. A homogeneous Ni-chiral-bisphosphine complex also catalyzes an efficient asymmetric hydrogenation of α-amino-β-keto ester hydrochlorides in an anti-selective manner. As a related process, the asymmetric hydrogenation of the configurationally stable substituted α-aminoketones using a Ni catalyst via DKR is also described. [ABSTRACT FROM AUTHOR]

Enantiomerically pure chiral amines are valuable building blocks for the synthesis of pharmaceutical drugs and agrochemicals. Indeed it is estimated that currently 40 % of pharmaceuticals contain a chiral amine component in their structure. Chiral amines are also widely used as resolving agents for diastereomeric salt crystallization. One of the challenges of preparing chiral amines in enantiomerically pure form is the development of cost-effective and sustainable catalytic methods that are able to address the requirement for the entire range of primary, secondary and tertiary amines. In this review we highlight various biocatalytic strategies that have been developed, particularly those based upon asymmetric synthesis or their equivalent therefore (i.e. dynamic kinetic resolution, deracemisation) in which yields and enantiomeric excesses approaching 100 % can be attained. Particular attention is given to the use of monoamine oxidase (MAO-N) from Aspergillus niger which has been engineered by directed evolution to provide a tool-box of variants which can generate enantiomerically pure primary, secondary and tertiary amines. These MAO-N variants are combined with non-selective chemical reducing agents in deracemisation processes. [ABSTRACT FROM AUTHOR]

Abstract: A strategy of nitrilase mediated dynamic kinetic resolution toward the synthesis of d-phenylglycine was developed, using aqueous-1-octanol biphasic system. Due to the efficient suppression of the decomposition of phenylglycinonitrile, a maximum yield of 81% is obtained. This result indicates that the nitrilase mediated dynamic kinetic resolution is a promising method toward the synthesis of d-phenylglycine and its derivatives. [Copyright &y& Elsevier]

ABSTRACT Chiral-center enantiomers have been shown to differ significantly in , pharmacodynamics, pharmacokinetics and toxicity. New developments in the organic synthesis have enriched the vast literature of synthetic methodologies applicable to access natural products as well as bioactive molecules. These compounds also include new drugs, drug candidates and reagents used to explore biological processes. The article reviews the synthesis of optically pure drugs, intermediates and amino alcohols by using different methods. Chirality 26:63-78, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: A novel and efficient racemization catalyst, Pd/layered double-hydroxide-dodecyl sulfate anion, was prepared and used in the dynamic kinetic resolution (DKR) of arylamines. The undesired enantiomer was completely racemized at 55°C, allowing the catalyst to be compatible with biocatalysts. DKR proceeded smoothly and showed a broad substrate scope, with good conversion and high product enantiomeric excesses (ee p). The system could be reused more than 30 times without loss of conversion and ee p value. [Copyright &y& Elsevier]

Surpassing nature: A hybrid catalyst in which Candida antarctica lipase B and a nanopalladium species are co‐immobilized into the compartments of mesoporous silica is presented. The metal nanoparticles and the enzyme are in close proximity to one another in the cavities of the support. The catalyst mimics a metalloenzyme and was used for dynamic kinetic resolution of a primary amine in high yield and excellent enantioselectivity. [ABSTRACT FROM AUTHOR]

Highlights: [•] Ru complexes/phosphotungstic acid/alumina were tested in dynamic kinetic resolution. [•] DKR of 1-phenylethanol proceeded well without alkali additive in n-octane over Ru-p-cymene. [•] Immobilized Ru complexes showed the highest activity without base in n-octane. [•] Process efficiency was influenced by the solvent, base, support and catalyst type. [ABSTRACT FROM AUTHOR]

Dynamic kinetic resolution of various homoallylic alcohols with the use of Candida antarctica lipase B and ruthenium catalyst 2 afforded homoallylic acetates in high yields and with high enantioselectivity. These enantiopure acetates were further transformed into homoallylic acrylates after hydrolysis of the ester function and subsequent DMAP-catalyzed esterification with acryloyl chloride. After ring-closing metathesis 5,6-dihydropyran-2-ones were obtained in good yields. Selective hydrogenation of the carboncarbon double bond afforded the corresponding δ-lactones without loss of chiral information. [ABSTRACT FROM AUTHOR]

Chiral β-hydroxysulfides are an important class of organic compounds which find broad application in organic and pharmaceutical chemistry. Herein we describe the development of novel biocatalytic and chemoenzymatic methods for the enantioselective synthesis of β-hydroxysulfides by exploiting ketoreductase (KRED) enzymes. Four KREDs were discovered from a pool of 384 enzymes identified and isolated through a metagenomic approach. KRED311 and KRED349 catalysed the synthesis of β-hydroxysulfides bearing a stereocentre at the C-O bond with opposite absolute configurations and excellent ee values by novel chemoenzymatic and biocatalytic-chemical-biocatalytic (bio-chem-bio) cascades starting from commercially available thiophenols/thiols and α-haloketones/alcohols. KRED253 and KRED384 catalysed the enantioselective synthesis of β-hydroxysulfides bearing a stereocentre at the C-S bond with opposite enantioselectivities by dynamic kinetic resolution (DKR) of racemic α-thioaldehydes., (© 2022 Wiley-VCH GmbH.)

In this paper we describe the chemoenzymatic synthesis of enantiopure l-2-arylthiazol-4-yl alanines starting from their racemic N-acetyl derivatives; by combining the lipase-catalysed dynamic kinetic resolution of oxazol-5(4H)-ones with a chemical and an enzymatic enantioselective hydrolytic step affording the desired products in good yields (74%–78%) and high enantiopurities (ee > 99%). The developed procedure exploits the utility of the single-walled carbon nanotubes-bound diethylaminoethanol as mild and efficient racemisation agent for the dynamic kinetic resolution of the corresponding oxazolones.

Herein we describe a short and practical synthesis of the exceptional musk odorants (R)-muscone and (R,Z)-5-muscenone from a readily available achiral macrocyclic diketone. The key step of the synthesis is the first sodium N-methylephedrate mediated enantioselective aldol condensation reaction (up to 76% ee). This new type of reaction proceeds via a dynamic kinetic resolution of an aldol intermediate.

Abstract: A convenient method for the enantioselective synthesis of β′-hydroxy-β-amino esters was developed through intensive investigations of the reaction conditions. Dichloromethane (DCM)/2,2,2-trifluoroethanol (TFE) and 1,2-dichloroethane (DCE)/TFE combinations were found to be the appropriate co-solvents for the reaction. In this mixed solvent system, [Ru(cymene)Cl2]2–Sunphos exhibited unusually higher activity and selectivity than the corresponding [Ru(cymene)I2]2–Sunphos. In situ generated catalyst could be used for this transformation. Asymmetric hydrogenation of a series of β′-keto-β-amino esters derivatives using Ru–Sunphos complexes via dynamic kinetic resolution led to the corresponding β′-hydroxy-β-amino esters with ee up to 99.6% and de up to 98.8% (S/C=1000). [Copyright &y& Elsevier]

An efficient catalytic asymmetric hydrogenation of racemic α-arylcyclohexanones with an ethylene ketal group at the 5-position of the cyclohexane ring via dynamic kinetic resolution has been developed, giving chiral α-arylcyclohexanols with two contiguous stereocenters with up to 99% ee and >99:1 cis/ trans-selectivity. Using this highly efficient asymmetric hydrogenation reaction as a key step, (−)-α-lycorane was synthesized in 19.6% overall yield over 13 steps from commercially available starting material. [ABSTRACT FROM AUTHOR]

Highlights: [•] Immobilization of His-tagged HLADH was successfully reported. [•] Effect of pH, temperature and organic co-solvents was investigated. [•] Application of the new imm-His-HLADH on the reduction of aldehydes was investigated. [•] Chemoenzymatic synthesis of enantiopure Profenols via DKR with His-HLADH was reported. [ABSTRACT FROM AUTHOR]

Amphiphilic poly(amine-co-ester)s, which contain a single effective enantiomer of an asymmetric drug and thus can avoid potentially serious side effects, are difficult to prepare through nonselective chemical routes not only in the process of introducing chiral drugs to the polymer, but also in the synthesis of the polymer's backbone by metal catalysts. A model of racemic mexiletine, an important antiarrhythmic agent, was used to demonstrate the tandem combination of Candida antarctica lipase B (CAL-B)- and Pd/C-catalyzed dynamic kinetic resolution (DKR) and subsequent CAL-B-catalyzed polycondensation, as an efficient protocol to prepare poly(ethylene glycol)-functionalized poly(amine-co-ester)s containing (R)-mexiletine with 99% ee value. Chemoenzymatic DKR and enzymatic polymerization conditions were optimized, and the optical purity of incorporated (R)-mexiletine was confirmed through its hydrolysis from polyester. The copolymers can readily self-assemble into nanometer-scale-sized micelles with well-dispersed spheres, which have a size distribution that can be efficiently adjusted by changing the polymer concentration. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013 [ABSTRACT FROM AUTHOR]

V for resolution: A new oxovanadium catalyst (V‐MPS; see scheme) immobilized in the pores of mesoporous silica has been developed. The combined use of V‐MPS and lipases achieved the dynamic kinetic resolution of a wide range of racemic alcohols (1 or 2) to produce optically active esters 3 in high chemical and optical yields. The paired catalysts retained high catalytic activity when reused up to six times. [ABSTRACT FROM AUTHOR]

Chiral diols with three contiguous stereocenters were synthesized by a highly enantioselective ruthenium‐catalyzed asymmetric hydrogenation of racemic α,α′‐disubstituted cycloketones involving dynamic kinetic resolution. This new catalytic asymmetric method provides a concise route to the alkaloid (+)‐γ‐lycorane. [ABSTRACT FROM AUTHOR]

Biocatalyzed asymmetric reduction of ketones is an environmentally friendly approach and one of the most cost-effective routes for producing chiral alcohols. In comparison with the well-studied reduction of prochiral ketones to generate chiral alcohols with one chiral center, resolution of racemates by ketoreductases (KREDs) to produce chiral compounds with at least two chiral centers is also an important strategy in asymmetric synthesis. The development of protein engineering and the combination with chemo-catalysts further enhanced the application of KREDs in the efficient production of chiral alcohols with high stereoselectivity. This review discusses the advances in the research area of KRED catalyzed asymmetric synthesis for biomanufacturing of chiral chemicals with at least two chiral centers through the kinetic resolution (KR) approach and the dynamic kinetic resolution (DKR) approach., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Liu, Fang, Jia, Zheng, You and Qin.)

Mutant α-amino-ε-caprolactam (ACL) racemase (L19V/L78T) from Achromobacter obae with improved substrate specificity toward phenylalaninamide was obtained by directed evolution. The mutant ACL racemase and thermostable mutant D-amino acid amidase (DaaA) from Ochrobactrum anthropi SV3 co-expressed in Escherichia coli (pACLmut/pDBFB40) were utilized for synthesis of ( R)-phenylalanine and non-natural ( R)-phenylalanine derivatives (4-OH, 4-F, 3-F, and 2-F-Phe) by dynamic kinetic resolution (DKR). Recombinant E. coli with DaaA and mutant ACL racemase genes catalyzed the synthesis of ( R)-phenylalanine with 84% yield and 99% ee from ( RS)-phenylalaninamide (400 mM) in 22 h. ( R)-Tyrosine and 4-fluoro-( R)-phenylalanine were also efficiently synthesized from the corresponding amide compounds. We also co-expresed two genes encoding mutant ACL racemase and L-amino acid amidase from Brevundimonas diminuta in E. coli and performed the efficient production of various ( S)-phenylalanine derivatives. Moreover, 2-aminophenylpropionitrile was converted to ( R)-phenylalanine by DKR using a combination of the non-stereoselective nitrile hydratase from recombinamt E. coli and mutant ACL racemase and DaaA from E. coli encoding mutant ACL racemase and DaaA genes. [ABSTRACT FROM AUTHOR]

The development and further evolution of the first catalytic asymmetric conjugate additions of azlactones as activated amino acid derivatives to enones is described. Whereas the first-generation approach started from isolated azlactones, in the second-generation approach the azlactones could be generated in situ starting from racemic N-benzoylated amino acids. The third evolution stage could make use of racemic unprotected α-amino acids to directly form highly enantioenriched and diastereomerically pure masked quaternary amino acid products bearing an additional tertiary stereocenter. The step-economic transformations were accomplished by cooperative activation by using a robust planar chiral bis-Pd catalyst, a Brønsted acid (HOAc or BzOH; Ac=acetyl, Bz=benzoyl), and a Brønsted base (NaOAc). In particular the second- and third-generation approaches provide a rapid and divergent access to biologically interesting unnatural quaternary amino acid derivatives from inexpensive bulk chemicals. In that way highly enantioenriched acyclic α-amino acids, α-alkyl proline, and α-alkyl pyroglutamic acid derivatives could be prepared in diastereomerically pure form. In addition, a unique way is presented to prepare diastereomerically pure bicyclic dipeptides in just two steps from unprotected tertiary α-amino acids. [ABSTRACT FROM AUTHOR]

The development of new and more economically and environmentally attractive processes to afford chiral molecules is still an open challenge in organic synthesis. During last years the combination of an enzyme-catalyzed kinetic resolution (KR) with the in situ transition metal mediated-racemization of the unreacted enantiomer in a dynamic kinetic resolution (DKR) has received great attention in the preparation of enantiomerically pure compounds, as this methodology allows one to achieve very high conversions and enantiomeric excesses. Several transition metal complexes have been found to be compatible with enzymatic catalysts and highly successful DKR processes of functionalized alcohols and amines have been developed. Those chemicals are valuable building blocks for the further production of many pharmaceuticals and fine chemicals. The aim of this review is to update the advances developed during the past decade related to the coupling of enzymes and transition metal catalysts in DKR processes, focusing on the application of this innovative technique in the synthetic route of biologically active compounds. [ABSTRACT FROM AUTHOR]