Racemic acid resolution


Resolution of Racemic Acid.—The racemic acid is dissolved in water (250 c.c.) and divided into two equal volumes. Half of the solution is carefully neutralised with caustic soda and the other half with ammonia, and the two solutions then mixed.  [c.123]

The separation of a racemic mixture into its enantiomeric components is termed resolution The first resolution that of tartaric acid was carried out by Louis Pasteur m 1848 Tartaric acid IS a byproduct of wine making and is almost always found as its dextrorotatory 2R 3R stereoisomer shown here m a perspective drawing and m a Fischer projection  [c.310]

Crystallization Method. Such methods as mechanical separation, preferential crystallisation, and substitution crystallisation procedures are included in this category. The preferential crystallisation method is the most popular. The general procedure is to inoculate a saturated solution of the racemic mixture with a seed of the desired enantiomer. Resolutions by this method have been reported for histidine (43), glutamic acid (44), DOPA (45), threonine (46), A/-acetyl phenylalanine (47), and others. In the case of glutamic acid, the method had been used for industrial manufacture (48).  [c.278]

Enzymatic hydrolysis of A/-acylamino acids by amino acylase and amino acid esters by Hpase or carboxy esterase (70) is one kind of kinetic resolution. Kinetic resolution is found in chemical synthesis such as by epoxidation of racemic allyl alcohol and asymmetric hydrogenation (71). New routes for amino acid manufacturing are anticipated.  [c.279]

The P CD column exhibits excellent selectivity for enantiomers of certain amino acid derivatives. Underivatized amino acids are apparentiy too small to biad tightly to the P CD cavity and show no enantiomeric resolution. When a substituent such as a dansyl group is present on the amino acid, strong iaclusion complexes with P CD are formed and baseline separation is achieved (see Table 2) (10). Either the amino or the carboxylate group of the amino acid can be derivatized to obtain chiral recognition. Derivatization of both groups, however, tends to reduce chiral recognition. It is possible to detect as Httie as 0.2% of one enantiomer ia a racemic mixture as shown ia Figure 2b, thus providing an extremely sensitive test of optical purity (5).  [c.98]

The separation of a racemic mixture into its enantiomeric components is termed resolution. The first resolution, that of tartaric acid, was carried out by Louis Pasteur in 1848. Tartaric acid is a byproduct of wine making and is almost always found as its dextrorotatory 2R, iR stereoisomer, shown here in a perspective drawing and in a Fischer projection.  [c.310]

The improvements in resolution achieved in each deconvolution step are shown in Figure 3-3. While the initial library could only afford a modest separation of DNB-glutamic acid, the library with proline in position 4 also separated DNP derivatives of alanine and aspartic acid, and further improvement in both resolution and the number of separable racemates was observed for peptides with hydrophobic amino acid residues in position 3. However, the most dramatic improvement and best selectivity were found for c(Arg-Lys-Tyr-Pro-Tyr-(3-Ala) (Scheme 3-2a) with the tyrosine residue at position 5 with a resolution factor as high as 28 observed for the separation of DNP-glutamic acid enantiomers.  [c.66]

Acetophenone similarly gives an oxime, CHjCCgHjlCtNOH, of m.p. 59° owing to its lower m.p. and its greater solubility in most liquids, it is not as suitable as the phenylhydrazone for characterising the ketone. Its chief use is for the preparation of 1-phenyl-ethylamine, CHjCCgHslCHNHj, which can be readily obtained by the reduction of the oxime or by the Leuckart reaction (p. 223), and which can then be resolved by d-tartaric acid and /-malic acid into optically active forms. The optically active amine is frequently used in turn for the resolution of racemic acids.  [c.258]

The 9 — 15 fragment was prepared by a similar route. Once again Sharpless kinetic resolution method was applied, but in the opposite sense, i.e., at 29% conversion a mixture of the racemic olefin educt with the virtually pure epoxide stereoisomer was obtained. On acid-catalysed epoxide opening and lactonization the stereocentre C-12 was inverted, and the pure dihydroxy lactone was isolated. This was methylated, protected as the acetonide, reduced to the lactol, protected by Wittig olefination and silylation, and finally ozonolysed to give the desired aldehyde.  [c.322]

Unless a resolution step is included the a ammo acids prepared by the synthetic methods just described are racemic Optically active ammo acids when desired may be obtained by resolving a racemic mixture or by enantioselective synthesis A synthesis IS described as enantioselective if it produces one enantiomer of a chiral compound m an amount greater than its mirror image Recall from Section 7 9 that optically inactive reactants cannot give optically active products Enantioselective syntheses of ammo acids therefore require an enantiomerically enriched chiral reagent or catalyst at some point m the process If the chiral reagent or catalyst is a single enantiomer and if the reaction sequence is completely enantioselective an optically pure ammo acid is obtained Chemists have succeeded m preparing a ammo acids by techniques that are more than 95% enantioselective Although this is an impressive feat we must not lose sight of the fact that the enzyme catalyzed reactions that produce ammo acids m living systems do so with 100% enantioselectivity  [c.1122]

Following this line, a great variety of optically resolved (optically active) crown compounds were prepared for the resolution of racemic cationic substrates, eg, chiral primary ammonium salts, protonated a-aminoalcohols and a-amino acid derivatives, through complexation (137—139). Among the highest enantiomer recognition properties for chiral ammonium ions were obtained with crown ethers having one or two 1,1-binaphthyl chiral barriers in the framework (Fig. 23a) (27,37,140). Others contain a spirobifluotene chiral subunit (141) or ate derived from terpenoids, amino acids, and hydroxy acids that make use of the natural pool of chiral compounds (138). Typical examples for the latter classes of receptors are shown in Figure 23b, c where natural a-D-glucose (142) or tartaric acid (143) are the chiral sources. A further important family of chiral receptors derived from natural glucose are the cyclodextrins (Fig. 15a) (93—95). Moreover, most of these receptors (cf. Fig. 23a—c) are carefully designed systems in that they contain at least one axis of symmetry (dissymmetric compound type), a tactic that makes the receptors nonsided with respect to perching substrates, eg, ammonium guests (136). Beyond that symmetric receptor molecules have also been used to advantage in chiral recognition such as the cryptophane in Figure 16a (101,102) or the basket shaped chiral host presented in Figure 23d (144). Although besides chiral ammonium ions amides are the substrate class of compounds to be very efficiendy resolved by the majority of receptors, particular enantiomer recognition properties including steroid hormones have also been reported (145).  [c.187]

In a similar way, several cephalosporins have been hydrolyzed to 7-aminodeacetoxycephalosporanic acid (72), and nocardicin C to 6-aminonocardicinic acid (73). Penicillin G amidase from Pscherichia coli has been used in an efficient resolution of a racemic cis intermediate required for a preparation of the synthon required for synthesis of the antibiotic Loracarbef (74). The racemic intermediate (21) underwent selective acylation to yield the cis derivative (22) in 44% yield the product displayed a 97% enantiomeric excess (ee).  [c.311]

Resolution Methods. Chiral pharmaceuticals of high enantiomeric purity may be produced by resolution methodologies, asymmetric synthesis, or the use of commercially available optically pure starting materials (44,45). Resolution refers to the separation of a racemic mixture. Classical resolutions involve the constmction of a diastereomer by reaction of the racemic substrate with an enantiomerically pure compound. The two diastereomers formed possess different physical properties and may be separated by crystallization (qv), chromatography (qv), or distillation (qv). A disadvantage of the use of resolutions is that the best yield obtainable is 50%, which is rarely approached. However, the yield may be improved by repeated racemization of the undesired enantiomer and subsequent resolution of the racemate. Resolutions are commonly used in industrial preparations of homochiral compounds (16). Chiral acids and amines are generally separable by crystallization of the diastereomeric salts formed with an appropriate optically pure amine or acid, respectively (46). Racemic mixtures of mandelic acid (27) are resolved by treatment with optically pure (R)-(+)-methy1henzy1amine (28) and formation of the diastereomeric salts (29) and (30). (R)-(—)-MandeHc acid selectively crystallizes with (R)-(+)-methy1henzylamine (28) and is isolated by simple filtration.  [c.241]

Three general methods exist for the resolution of enantiomers by Hquid chromatography (qv) (47,48). Conversion of the enantiomers to diastereomers and subsequent column chromatography on an achiral stationary phase with an achiral eluant represents a classical method of resolution (49). Diastereomeric derivatization is problematic in that conversion back to the desired enantiomers can result in partial racemization. For example, (lR,23, 5R)-menthol (R)-mandelate (31) is readily separated from its diastereomer but ester hydrolysis under numerous reaction conditions produces (R)-(-)-mandehc acid (32) which is contaminated with (3)-(+)-mandehc acid (33).  [c.241]

One of the homochiral starting materials (45) for the acetylcholinesterase (ACE) inhibitor captopril [62571 -86-2] (47) is produced by a Hpase enzyme-catalyzed resolution of racemic 3-methyl-4-acetylthiobutyric acid (44) and L-proline (46) (65).  [c.242]

This procedure is restricted mainly to aminodicarboxyhc acids or diaminocarboxyhc acids. In the case of neutral amino acids, the amino group or carboxyl group must be protected, eg, by A/-acylation, esterification, or amidation. This protection of the racemic amino acid and deprotection of the separated enantiomers add stages to the overall process. Furthermore, this procedure requires a stoichiometric quantity of the resolving agent, which is then difficult to recover efficiendy. Practical examples of resolution by this method have been pubUshed (50,51).  [c.278]

Despite the progress made in the stereoselective synthesis of (R)-pantothenic acid since the mid-1980s, the commercial chemical synthesis still involves resolution of racemic pantolactone. Recent (ca 1997) synthetic efforts have been directed toward developing a method for enantioselective synthesis of (R)-pantolactone by either chemical or microbial reduction of ketopantolactone. Microbial reduction of ketopantolactone is a promising area for future research.  [c.63]

Because diastereoisomers have different physical and chemical properties, they can be separated by a range of chemical and physical methods. The process of resolution is the sqjaration of a racemic mixture. Separation is frequently effected by converting the enantiomers into a mixture of diastereomers by reaction with a pure enantiomer of a second reagent, the resolving agentP Because the two resulting products will be diastereomeric, they can be separated. The separated diastereomers can then be reconverted to the pure enantiomers by reversing the initial chemical transformation. An example of this method is shown in Scheme 2.4 for the resolution of a racemic carboxylic acid by way of a diastereomeric salt resulting from reaction with an enantiomerically pure amine. The / -acid, / -amine and S-acid, / -amine salts are separated by fractional recrystallization. The resolved acids are regenerated by reaction with a strong acid, which liberates the carboxylic acid from the amine salt.  [c.88]

Unless a resolution step is included, the a-anino acids prepared by the synthetic methods just described are racemic. Optically active amino acids, when desired, may be obtained by resolving a racemic mixture or by enantioselective synthesis. A synthesis is described as enantioselective if it produces one enantiomer of a chiral compound in an amount greater than its minor image. Recall from Section 7.9 that optically inactive reactants cannot give optically active products. Enantioselective syntheses of amino acids therefore require an enantiomerically enriched chiral reagent or catalyst at some point in the process. If the chiral reagent or catalyst is a single enantiomer and if the reaction sequence is completely enantioselective, an optically pure amino acid is obtained. Chemists have succeeded in preparing a-anino acids by techniques that are more than 95% enantioselective. Although this is an impressive feat, we must not lose sight of the fact that the enzyme catalyzed reactions that produce amino acids in living systems do so with 100% enantioselectivity.  [c.1122]

With regard to the resolution of enantiomers, some applications can be found with modified silica gel supports. Thus, a Pirkle-type CSP was used for the separation of 200 mg of a racemic benzodiazepinone [75]. Also tris-(3,5-dimethylphenyl)carba-mate of cellulose coated on silica [91, 92] was applied successfully to the resolution of the enantiomers of 2-phenoxypropionic acid and to oxprenolol, alprenolol, propranolol among other basic drugs. However, the low efficiency of this technique and the relative high price of the CSPs limits its use to the resolution of milligram range of sample.  [c.7]

However, it was not until the beginning of 1994 that a rapid (<1.5 h) total resolution of two pairs of racemic amino acid derivatives with a CPC device was published [124]. The chiral selector was A-dodecanoyl-L-proline-3,5-dimethylanilide (1) and the system of solvents used was constituted by a mixture of heptane/ethyl acetate/methanol/water (3 1 3 1). Although the amounts of sample resolved were small (2 ml of a 10 inM solution of the amino acid derivatives), this separation demonstrated the feasibility and the potential of the technique for chiral separations. Thus, a number of publications appeared subsequently. Firstly, the same chiral selector was utilized for the resolution of 1 g of ( )-A-(3,5-dinitrobenzoyl)leucine with a modified system of solvents, where the substitution of water by an acidified solution  [c.10]

Most of the chiral membrane-assisted applications can be considered as a modality of liquid-liquid extraction, and will be discussed in the next section. However, it is worth mentioning here a device developed by Keurentjes et al., in which two miscible chiral liquids with opposing enantiomers of the chiral selector flow counter-currently through a column, separated by a nonmiscible liquid membrane [179]. In this case the selector molecules are located out of the liquid membrane and both enantiomers are needed. The system allows recovery of the two enantiomers of the racemic mixture to be separated. Thus, using dihexyltartrate and poly(lactic acid), the authors described the resolution of different drugs, such as norephedrine, salbu-tamol, terbutaline, ibuprofen or propranolol.  [c.15]

Synthetic polymers. In the 1970s, Blaschke prepared several crosslinked gels from N-acryloylated L-amino acids and a small percentage of ethylene dimethacrylate or divinylbenzene and used them for the low-pressure chromatographic resolution of racemic amino acid derivatives and mandelic acid [23]. Another polymer-based CSP was later prepared by Okamoto from isotactic poly(triphenylmethyl methacrylate). This material is the prototypical polymeric selector with a well-defined one-handed helical structure [24]. This polymer was prepared by anionic polymerization using a chiral organolithium initiator, and then coated onto porous silica beads. While these columns were successful in the separation of a broad variety of racemates, their relative lack of chemical stability and high cost make them less suitable for large-scale applications.  [c.58]

Since the proline residue in peptides facilitates the cyclization, 3 sublibraries each containing 324 compounds were prepared with proline in each randomized position. Resolutions of 1.05 and 2.06 were observed for the CE separation of racemic DNP-glutamic acid using peptides with proline located on the first and second random position, while the peptide mixture with proline preceding the (i-alamine residue did not exhibit any enantioselectivity. Since the c(Arg-Lys-0-Pro-0-(i-Ala) library afforded the best separation, the next deconvolution was aimed at defining the best amino acid at position 3. A rigorous deconvolution process would have required the preparation of 18 libraries with each amino acid residue at this position.  [c.64]

Amino acid separations represent another specific application of the technology. Amino acids are important synthesis precursors - in particular for pharmaceuticals -such as, for example, D-phenylglycine or D-parahydroxyphenylglycine in the preparation of semisynthetic penicillins. They are also used for other chiral fine chemicals and for incorporation into modified biologically active peptides. Since the unnatural amino acids cannot be obtained by fermentation or from natural sources, they must be prepared by conventional synthesis followed by racemate resolution, by asymmetric synthesis, or by biotransformation of chiral or prochiral precursors. Thus, amino acids represent an important class of compounds that can benefit from more efficient separations technology.  [c.217]


See pages that mention the term Racemic acid resolution : [c.258]    [c.320]    [c.190]    [c.313]    [c.242]    [c.339]    [c.286]    [c.58]    [c.91]    [c.418]    [c.15]    [c.53]   
Practical organic chemistry (0) -- [ c.123 ]