Amino acids optically active enantiomers

During polymerization of (R3 )-2-(phenoxymethyl)thiirane by diethylzinc/L-amino acid, the S-enantiomer of the thiirane was consumed preferentially <2002PSA3443>. Synthesis of optically active polymers prepared from thiiranes was described <2005TA2149>. 

For the stereochemical determination, it seemed theoretically that the most efficient method of separation for the three pristane isomers A, B and C would be direct gas chromatography on an optically active stationary phase. Such a method was successfully employed for amino acids and amine enantiomers . However, this method was found ineffective for pristane, and hence various gas-chromatographic inactive stationary phases were employed for the separation of the diastereoisomers. The relative stereochemistry could be determined, provided standards with known respective stereochemistry are available. 

The separation of amino acids into particular enantiomers was the subject of mass spectrometric studies but also ESI MS was applied to determine by kinetic resolution the enantiomeric excess of optically active alcohols and amines in nanoscale by diastereoselective derivatization with optically active acids [38], This method has several distinctive features among others, easily available chiral acids can be used (the authors used A -benzoyl proline derivatives), no chromatographic separations are required, it is insensitive to certain impurities, it is fast and requires only small amount of substrate (10 nmol or less). The method can take an advantage when accuracy of enantiomeric excess measurement is sufficient within 10% limits. 

Photodriven reactions of Fischer carbenes with alcohols produces esters, the expected product from nucleophilic addition to ketenes. Hydroxycarbene complexes, generated in situ by protonation of the corresponding ate complex, produced a-hydroxyesters in modest yield (Table 15) [103]. Ketals,presumably formed by thermal decomposition of the carbenes, were major by-products. The discovery that amides were readily converted to aminocarbene complexes [104] resulted in an efficient approach to a-amino acids by photodriven reaction of these aminocarbenes with alcohols (Table 16) [105,106]. a-Alkylation of the (methyl)(dibenzylamino)carbene complex followed by photolysis produced a range of racemic alanine derivatives (Eq. 26). With chiral oxazolidine carbene complexes optically active amino acid derivatives were available (Eq. 27). Since both enantiomers of the optically active chromium aminocarbene are equally available, both the natural S and unnatural R amino acid derivatives are equally... 

Chiral stationary phases for the separation of enantiomers (optically active isomers) are becoming increasingly important. Among the first types to be synthesized were chiral amino acids ionically or covalently bound to amino-propyl silica and named Pirkle phases after their originator. The ionic form is susceptable to hydrolysis and can be used only in normal phase HPLC whereas the more stable covalent type can be used in reverse phase separations but is less stereoselective. Polymeric phases based on chiral peptides such as bovine serum albumin or a -acid glycoproteins bonded to... 

The binding sites of most enzymes and receptors are highly stereoselective in recognition and reaction with optical isomers (J, 2 ), which applies to natural substrates and synthetic drugs as well. The principle of enantiomer selectivity of enzymes and binding sites in general exists by virtue of the difference of free enthalpy in the interaction of two optical antipodes with the active site of an enzyme. As a consequence the active site by itself must be chiral because only formation of a diasteromeric association complex between substrate and active site can result in such an enthalpy difference. The building blocks of enzymes and receptors, the L-amino acid residues, therefore ultimately represent the basis of nature s enantiomer selectivity. 

What are the facts of life One of the most striking is that all known living systems involve the same types of polymers, i.e., three varieties of homochiral biopolymers. That is, each variety is composed of unique molecular building blocks having the same three-dimensional handedness. Thus, with rare exceptions, the proteins found in cells are composed exclusively of the 1-enantiomers of 19 optically active amino acids (Fig. 11.1). Similarly, only D-ribose and 2-deoxy-D-ribose sugars are found in the nucleic acid polymers that make up the RNAs and DNAs, which are essential for protein synthesis in the cell and for the transmission of genetic information from one generation to the next. 

The complete transformation of a racemic mixture into a single enantiomer is one of the challenging goals in asymmetric synthesis. We have developed metal-enzyme combinations for the dynamic kinetic resolution (DKR) of racemic primary amines. This procedure employs a heterogeneous palladium catalyst, Pd/A10(0H), as the racemization catalyst, Candida antarctica lipase B immobilized on acrylic resin (CAL-B) as the resolution catalyst and ethyl acetate or methoxymethylacetate as the acyl donor. Benzylic and aliphatic primary amines and one amino acid amide have been efficiently resolved with good yields (85—99 %) and high optical purities (97—99 %). The racemization catalyst was recyclable and could be reused for the DKR without activity loss at least 10 times. 

OPA in combination with chiral thiols is one method used to determine amino acid enantiomers. A highly fluorescent diastereomeric isoindole is formed and can be separated on a reverse-phase column. Some of these chiral thiols include N-acetyl-L-cysteine (NAC), N-tert-butyloxy-carbonyl- L-cysteine (Boc-L-Cys), N-isobutyryl- L-cysteine (IBLC), and N-isobutyryl- D -cysteine (IBDC). Replacing OPA-IBLC with OPA-IBDC causes a reversal in the elution order of the derivatives of D- and L-amino acids on an ODS column (Hamase et al., 2002). Nimura and colleagues (2003) developed a novel, optically active thiol compound, N-(tert-butylthiocarbamoyl)- L-cysteine ethyl ester (BTCC). This reagent was applied to the measurement of D-Asp with a detection limit of approximately 1 pmol, even in the presence of large quantities of L-ASP. 

Serine hydroxymethyl transferase catalyzes the decarboxylation reaction of a-amino-a-methylmalonic acid to give (J )-a-aminopropionic acid with retention of configuration [1]. The reaction of methylmalonyl-CoA catalyzed by malonyl-coenzyme A decarboxylase also proceeds with perfect retention of configuration, but the notation of the absolute configuration is reversed in accordance with the CIP-priority rule [2]. Of course, water is a good proton source and, if it comes in contact with these reactants, the product of decarboxylation should be a one-to-one mixture of the two enantiomers. Thus, the stereoselectivity of the reaction indicates that the reaction environment is highly hydro-phobic, so that no free water molecule attacks the intermediate. Even if some water molecules are present in the active site of the enzyme, they are entirely under the control of the enzyme. If this type of reaction can be realized using synthetic substrates, a new method will be developed for the preparation of optically active carboxylic acids that have a chiral center at the a-position. 

Enantiomer separation on optically active amino acid, dipeptide, diamide and amide phases by association via hydrogen bonding. " ... 

Optically active aldehydes are available in abundance from amino and hydroxy acids or from carbohydrates, thereby providing a great variety of optically active nitrile oxides via the corresponding oximes. Unfortunately, sufficient 1,4- or 1,3-asymmetric induction in cycloaddition to 1-alkenes or 1,2-disubstituted alkenes has still not been achieved. This represents an interesting problem that will surely be tackled in the years to come. On the other hand, cycloadditions with achiral olefins lead to 1 1 mixtures of diastereoisomers, that on separation furnish pure enantiomers with two or more stereocenters. This process is, of course, related to the separation of racemic mixtures, also leading to both enantiomers with 50% maximum yield for each. There has been a number of applications of this principle in synthesis. Chiral nitrile oxides are stereochemicaUy neutral, and consequently 1,2-induction from achiral alkenes can fully be exploited (see Table 6.10). 

Since enzymes are proteins made up of optically active amino acids, enzymes are themselves optically active and therefore react with only one enantiomer of a chiral substrate. 

The a-carbon of each amino acid is attached to four different chemi cal groups and is, therefore, a chiral or optically active carbon atom. Glycine is the exception because its a-carbon has two hydro gen substituents and, therefore, is optically inactive. [Note Amino acids that have an asymmetric center at the a-carbon can exist in two forms, designated D and L, that are mirror images of each other (Figure 1.8). The two forms in each pair are termed stereoisomers, optical isomers, or enantiomers.] All amino acids found in proteins are of the L-configuration. However, D-amino acids are found in some antibiotics and in bacterial cell walls. (See p. 250 for a discus sion of D-amino acid metabolism.)... 

Chromatography with a chiral (optically active) stationary phase is one of the few ways to separate enantiomers. We can estimate ages of fossils up to 500 million years old by measuring the fraction of amino acid that has transformed into the d enantiomer in a fossil.4-5 Amino acids do not have enough vapor pressure for gas chromatography. A volatile derivative suitable for gas chromatography is shown in the figure above.6... 

The resolution of optically active compounds by gas chromatography with chiral phases is a well-established procedure, and the separation of IV-perfluoro-acetylated amino acid ester enantiomers in 1967 was the first successful application of enantioselective gas-liquid chromatography [39] Amino acids have been resolved as their A-trifluoroacetyl esters on chiral diamide phases such as N-lauroyl-L-valine rerr-butylamide or iV-docosanoyl-L-valine fert-butylamide [40,41,... 

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