Resolution Of Racemic Compounds Research Articles

Green Synthesis of Biorelevant Scaffolds through Organocatalytic/ Enzymatic Dynamic Kinetic Resolution.

This review highlights major developments in the application of green organocatalytic and enzymatic dynamic kinetic resolutions (DKRs) in the total synthesis of biorelevant scaffolds. It illustrates the diversity of useful bioactive products and intermediates that can be synthesized under greener and more economic conditions through the combination of the powerful concept of DKR, which allows the resolution of racemic compounds with up to 100% yield, with either asymmetric organocatalysis or enzymatic catalysis, avoiding the use of toxic and expensive metals. With the need for more ecologic synthetic technologies, this field will undoubtedly expand its scope in the future with the employment of other organocatalysts/enzymes to even more types of transformations, thus allowing powerful greener and more economic strategies to reach other biologically important molecules.

Separation of Diastereomers Taking Advantage for the Kinetic Control and Structure of Resolving Agent

Abstract The preparation of pure enantiomers of (1-methyl-2-phenyl)-ethylamine (A) is described. The resolution of racemic compound (A) was accomplished using half equivalent of tartaric acid. The purification of enantiomeric mixtures by a non-usual method are also described.

Biotechnological potential of lipases from Pseudomonas: Sources, properties and applications

Abstract Lipases from Pseudomonas are extracellular enzymes that play an important role in biotechnological and industrial processes, due to their application in biofuels, food and pharmaceutical industries. Therefore, this paper provides an overview about the main aspects of the lipases from Pseudomonas, regarding their catalytic characterization, production, immobilization and application in many reactions of high industrial interest. The catalytic characterization and production of the lipase will be discussed, including the main lipase properties available in the literature and the influence of media composion, making possible the optimization of lipase production. Based on the main features of the lipases from Pseudomonas , this review also explores the recent developments on strategies of immobilization in order to enable recovery operations of the biocatalyst. The application of lipases to production of many high added-value products through esterifications, hydrolysis reactions and resolution of racemic compounds was also explored. The high yield and enantioselectivity of their reactions, regarding the resolution of racemic mixtures, shows that the lipases from Pseudomonas are efficient biocatalysts for biotechnological processes.

ChemInform Abstract: Recent Developments in Organocatalytic Dynamic Kinetic Resolution

AbstractReview: [62 refs.

Progress in membrane liquid–liquid reactor—a review

Liquid–liquid reactions are crucial in chemical synthesis and industries, such as hydrolysis, oxidation, reduction, nitration, and sulfonation of organic compounds. In recent years, membrane liquid–liquid reactors have drawn great attentions due to the elevated conversion, selectivity, yield, and efficiency. Membrane liquid–liquid reactors can be divided into membrane dispersive reactor and membrane non-dispersive reactor. The membrane dispersive reactor has been employed in the preparation of polymer microspheres and microcapsules. The non-dispersive membrane reactors are widely used in chemical reactions (e.g. consecutive, reversible, and irreversible reactions) and biochemical reactions (e.g. resolution of racemic compounds, and reaction of non-chiral substrate). The feature, applications, advantages, and limits of the membrane liquid–liquid reactors are briefly reviewed.

ChemInform Abstract: Access to the cis‐Fused Stereoisomers of Proline Analogues Containing an Octahydroindole Core.

AbstractReview: ca. 120 refs.

Steric effects on the enantiodiscrimination of diproline chiral stationary phases in the resolution of racemic compounds

Eight diproline chiral stationary phases with different end-capping groups were prepared and evaluated for the enantio-selective resolution of 41 racemic analytes. The end-capping group on the N-terminal of the peptide proved to be important as the chiral separation efficiency was decreased significantly without it. In general, increasing steric bulkiness near the N-terminal of diproline increases the enantioselectivity. Electronic structures of the end-capping groups are also important. One stationary phase with an adamantanecarbonyl capping group was found to provide both higher average separation and resolution factors than our previous leader. Three other stationary phases with 2-methylpropanoyl, cyclopropanecarbonyl and cyclobutanecarbonyl end capping groups were found to provide comparable average separation factor but higher resolution factors than our previous leader.

ChemInform Abstract: Organocatalyzed Dynamic Kinetic Resolution.

AbstractReview: 100 refs.

Organocatalyzed Dynamic Kinetic Resolution

AbstractIn the last decade, the first examples of organocatalyzed dynamic kinetic resolution (DKR) processes have been described, considerably expanding the synthetic scope of this powerful process which allows the resolution of racemic compounds with up to 100% yield. Today, a significant number of chiral organocatalysts are available that afford excellent levels of stereocontrol in various reactions evolving through DKR that could only previously be achieved using biocatalysts. The goal of the present review is to cover the works dealing with organocatalytic reactions evolving through DKR. This review is subdivided into four sections, according to the different types of organocatalysts employed in these reactions, such as Cinchona alkaloid catalysts, catalysts derived from amino acids, hydroxy acid catalysts, and miscellaneous organocatalysts.Abbreviations: Ac: acetyl; Ar: aryl; BINOL: 1,1′‐bi‐2‐naphthol; Bn: benzyl; Bu: butyl; c: cyclo; Cbz: benzyloxycarbonyl; CPME: cyclopentyl methyl ether; Cy: cyclohexyl; DABCO: 1,4‐diazabicyclo[2.2.2]octane; de: diastereomeric excess; DKR: dynamic kinetic resolution; DMF: dimethylformamide; Dmpe: 1,2‐bis(dimethylphosphino)‐ethane; DMSO: dimethyl sulfoxide; DYKAT: dynamic kinetic asymmetric transformation; ee: enantiomeric excess; Et: ethyl; Fmoc: 9‐fluorenylmethoxycarbonyl; Fu: furyl; Me: methyl; MTBE: methyl tert‐butyl ether; Naph: naphthyl; Pent: pentyl; Ph: phenyl; PMP: p‐methoxyphenyl; Pr: propyl; TBHP: tert‐butyl hydroperoxide; TEA: triethylamine; THF: tetrahydrofuran; Thio: thiophene; TMS: trimethylsilyl; Tol: tolyl.

Access to the cis‐Fused Stereoisomers of Proline Analogues Containing an Octahydroindole Core

AbstractAn overview of the synthetic methods developed to build all the cis‐fused stereoisomers of octahydroindole‐2‐carboxylic acid and its α‐methylated derivative in enantiomerically pure form is presented. Both asymmetric synthetic strategies(auxiliary‐ or substrate‐controlled processes) and procedures based on the resolution of racemic compounds (chemical, enzymatic, and chromatographic processes) are summarized. Special emphasis has been placed on those strategies able to provide multigram quantities of enantiopure compounds, a prerequisite to make downstream biological applications feasible.

A rapid and efficient method for directed screening of lipase-producing Burkholderia cepacia complex strains with organic solvent tolerance from rhizosphere

Lipase from Burkholderia cepacia strain is one of the most versatile biocatalysts and is used widely in many biotechnological application fields including detergent additives, the resolution of racemic compounds, etc. Based on the known whole genomic information of B. cepacia strain, both ampicillin and kanamycin were added to the TB-T medium to screen B. cepacia complex stains from rhizosphere soil samples. The selected colonies from the modified TB-T medium were then qualitatively determined the ability to produce extracellular lipase on the rhodamine B-olive oil agar plates. A total of 35 lipolytic pseudo-B. cepacia complex strains were isolated and the positive rate of lipolytic bacteria was 65%. Among them, 15 pseudo-B. cepacia complex strains showed tolerance to benzene, n-hexane and n-heptane at concentration of 10% (V/V) and were identified by the recA gene sequence. All of the 14 lipolytic bacteria were identified as B. cepacia complex strains except that the recA gene sequence of one lipolytic bacterium, strain ZMB009, was not obtained.

A Novel Method for Synthesis of Chiral Polymer Useful for Membrane Application

A Chiral polymer from 1,2-bis(2-methyl-1-triethylsiloxy-1-propenyloxy)ethane and dialdehyde from adipoyl chloride and 4-hydroxy benzaldehyde has been prepared in gram scale level and characterized by IR, NMR, TGA, DSC, optical rotation and Circular dichrosm (CD) study. The same was used for preparation of enantioselective membrane by phase inversion technique and the membrane was characterized for pore size and surface morphology through SEM (Scanning Electron Microscope) analysis. The enantioselective property of the membrane in the resolution of racemic compounds was studied using aqueous solution of Atenolol, Captopril, Propranolol hydrochloride and Salbutamol as feed solution. Pressure driven membrane processes were studied under pressure 4.84 × 10−2N/m2, 24.22 × 10−2N/m2 and 48.44 × 10−2N/m2. The Effect of feed concentration and operating pressure on membrane performance were studied differently. Solution diffusion model have been used to explain the permeation behaviour of the membrane. From this type of membrane 95% ee and 6.4mg/m2 h of flux were obtained.

Chiral HPLC for efficient resolution of enantiomers

Resolution of racemic compounds is one of the potential ways of obtaining both enantiomers. Among several resolution techniques in the past few decades, direct enantioseparation by high-performance liquid chromatography (HPLC) has significantly advanced, and a large number of chiral stationary phases (CSPs) for HPLC have been developed using both chiral small molecules and polymers with chiral recognition abilities. In this tutorial review, after describing the brief history and general view of CSPs, special emphasis will be placed on the studies involving the development and application of polysaccharide-based CSPs in our group.

Modeling of two separate phase enzyme membrane reactors for kinetic resolution of naproxen ester

Enzyme membrane reactors are described case by case on considering membrane properties, enzymes, immobilization methods and operation modes such as mono/multiphases [1]. In practical application, they will be detailed chosen in order to make the integrated system performing in optimal conditions. To do this, an appropriate mathematical modeling is necessary in order to assess the influence of various parameters on the reactor performance, e.g., enzyme concentration, enzymatic activity, and diffusion coefficients of the substrates through the loaded membrane fibers. The reactor performance can be evaluated in advance based on the established models considering the diffusion of substrates, reactant consumption and product formation. In most cases, the modeled differential equations might be solved analytically or numerically with respect to the boundary conditions matching the membrane bioreactor operating conditions [2]. Some important studies have been described in previous works [3]; however, few theoretical studies on the enzymatic kinetic resolution of racemic compounds in the two-separate phase enzyme membrane reactor (TSP-EMR) have been reported [2]. In this work, the modeling of a multiphase reactor using immobilized lipase to carry out the hydrolysis of racemic ester has been developed considering mass transfer properties measured in a previous study [4]. The modeling and experimental results will be compared.

Effect of the presence of a free hydroxyl group on the enantiodiscrimination properties of cholic acid based CSPs bearing 2-naphthylcarbamate and 3,5-dinitrophenylcarbamate moieties in the HPLC resolution of racemic compounds

Two new chiral selectors, obtained by derivatizing two of the three hydroxyl groups of cholic acid with 2-naphthylisocyanate and 3,5-dinitrophenylisocyanate, have been prepared and linked to silica gel to obtain chiral stationary phases (CSPs) for the HPLC separation of enantiomers. The enantiodiscriminating capability of the two CSPs has been compared to that of the analogous CSP obtained from an exhaustively derivatized cholic acid based selector, in order to establish the effect of the presence of a free hydroxyl group on the enantiodiscrimination properties of this kind of selector. The chromatographic results demonstrate that the enantioselectivity of these selectors strongly depends on the position of the hydroxyl group on the cholestanic backbone.

( S )‐Leucine and [( S )‐1‐(1‐Naphthyl)ethyl]amine as Chiral Building Blocks for a Bifunctional System − Synthesis of a New Chiral Stationary Phase and Evaluation of Its Biselector Properties in the HPLC Resolution of Racemic Compounds

Two selectors derived from [(S)-1-(1-naphthyl)ethyl]amine and (S)-leucine have been chemically bonded to one another and the resulting chiral auxiliary linked covalently to silica gel, to produce a new chiral stationary phase (CSP) for the HPLC resolution of enantiomers. The CSP is able to separate the enantiomers of some selected racemic compounds: both those resolved by Oi’s CSP {derived from [1-(1-naphthyl)ethyl]amine} and those enantiodiscriminated by Pirkle’s CSP [derived from N-(3,5-dinitrobenzoyl)leucine]. The results obtained demonstrate that the CSP possesses the properties of an efficient biselector system.

Captopril and its synthesis from chiral intermediates

AbstractCaptopril is an antihypertensive agent that inhibits the angiotensin‐converting enzyme of the renin–angiotensin system. Chiral intermediates are used in the synthesis of the drug. These intermediates are obtained by resolution of racemic compounds or by chemical, biocatalytic methods and or by asymmetric synthesis by biocatalytic process. This article reviews the various chemical and biochemical processes involved in the synthesis of the chiral drug, including the pharmacological action of captopril.© 2001 Society of Chemical Industry

Prolonged retention of cross-linked trypsin in calcium alginate microspheres

Trypsin microencapsulated in a calcium alginate matrix was lost quickly through diffusion when the microspheres were placed in an aqueous medium. This problem was overcome by first reacting trypsin with glutaraldehyde to form cross-linkages and then incorporating the enzyme in the alginate micro-spheres. The performance of the cross-linked trypsin remained optimal at pH 8 while it was found to be more heat-stable and remained highly active even at 80°C. Esters and amides of L-arginine were preferentially hydrolysed by the enzyme indicating that cross-linking did not adversely affect the conformation of the active site. There was a suppression in enzymatic activity when the microspheres were placed in reaction media with an increasing concentration of organic solvent such as ethanol, acetonitrile or isopropanol. However, when returned to a totally aqueous environment, the enzyme resumed its initial tryptic capability. Such a microencapsulated form of cross-linked enzyme may find application in enzyme replacement therapy, optical resolution of racemic compounds as well as organic synthesis in an aqueous-organic environment.

Chiral Chromatographic Discrimination Ability of a Cellulose 3,5-Dimethylphenylcarbamate/10-Undecenoate Mixed Derivative Fixed on Several Chromatographic Matrices

Abstract The properties as chiral selector in HPLC chiral stationary phases (CSPs) of a cellulose derivative bearing simultaneously 3,5-dimethylphenylamino carbonyl and 10-undecenoyl groups are described. This polysaccharide is reticulated (or bonded) on chromatographic supports such as silica gel, previously treated or not, graphite or alumina. The chiral stationary phases thus obtained are resistant to the usual solvents used in liquid chromatography and can be used on normal or reversed phase conditions. The results obtained on the resolution of racemic compounds with these stationary phases depend on the nature of the support. The best results were obtained with the chiral stationary phase in which the cellulose derivative is bonded on allyl silica gel.

Comparison between silica-bonded chiral stationary phases derived from 3,5-disubstituted N-benzoyl-( S)-phenylalanine and ( S)-cyclohexylalanine in the resolution of racemic compounds by liquid chromatography

A study was made of the role of the phenylalanine phenyl ring in the enantioselectivity of several chiral stationary phases (CSPs) whose chiral selectors consist of several N-(3,5-disubstituted)benzoyl derivatives of this amino acid covalently bonded to silica gel. Racemic compounds with π-acceptor, π-donor or both characters were resolved on two series of CSPs derived from N-(3,5-dimethyl)benzoyl, N-(3,5-dimethoxy)benzoyl) and N-(3,5-dinitro)benzoyl-( S)-phenylalanine and ( S)-cyclohexylalanine. In all instances the best enantioselectivities were obtained with CSPs derived from ( S)-cyclohexylalanine. The results show that the phenyl ring in the phenylalanine moiety does not have an electronic role in the recognition of the racemic compound by the chiral selector on the CSP, a non-classical π-π interaction between the 3,5-dinitrobenzoyl group in the racemic compound and in the CSP acts in the resolution of N-(3,5-dinitro)benzoyl derivatives of amino acids on CSPs with the same group and the change in the arrangement of solutes in the diastereomeric solute-stationary phase complexes can take place without an inversion of the elution order of enantiomers.