Enantiomers neutral

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). 

Early examples of enantioselective extractions are the resolution of a-aminoalco-hol salts, such as norephedrine, with lipophilic anions (hexafluorophosphate ion) [184-186] by partition between aqueous and lipophilic phases containing esters of tartaric acid [184-188]. Alkyl derivatives of proline and hydroxyproline with cupric ions showed chiral discrimination abilities for the resolution of neutral amino acid enantiomers in n-butanol/water systems [121, 178, 189-192]. On the other hand, chiral crown ethers are classical selectors utilized for enantioseparations, due to their interesting recognition abilities [171, 178]. However, the large number of steps often required for their synthesis [182] and, consequently, their cost as well as their limited loadability makes them not very suitable for preparative purposes. Examples of ligand-exchange [193] or anion-exchange selectors [183] able to discriminate amino acid derivatives have also been described. 

Bioassay of alternate molecular forms supports the view that the ORs are capable of resolving isomeric distinctions in neutral (non-biological) odourants. Stereochemical pairs of odours were tested for differential sensitivities in the blind subterranean mole rat (Spalax ehrenbergi). The subjects responded to one enantiomer, but not to its stereoisomer. Both sexes were attracted to the odour of R-(-)-carvone but unresponsive to S-(+)-carvone in contrast, males and females were repelled by the odour of (+)-citronellol, but not by (-)-citronellol (Heth et al., 1992). The lack of responsiveness by mole rats could be central due to lack of salience, or peripheral due to hyposmia/anosmia for one isomer. Both carvones have distinct odours for the human nose. 

Nishi et al. [110] used dextran and dextrin as chiral selectors in capillary-zone electrophoresis. Polysaccharides such as dextrins, which are mixtures of linear a-(l,4)-linked D-glucose polymers, and dextrans, which are polymers of D-glucose units linked predominantly by a-(l,6) bonds, have been employed as chiral selectors in the capillary electrophoretic separation of enantiomers. Because these polymers are electrically neutral, the method is applicable to ionic compounds. The enantiomers of basic or cationic drugs such as primaquine were successfully separated under acidic conditions. The effects of molecular mass and polysaccharide concentration on enantioselectivity were investigated. 

The above examples demonstrate the behavior of peptide bonds at neutral pH. Information is also available on the pH-rate profile of hydrolysis of peptide bonds, as exemplified by N-(phenylacetyl)glycyl-D-valine (6.47), an acyclic penicillin G analogue [69], As a preliminary observation, we note that this compound contains a single stereogenic center, meaning that results obtained with its enantiomer A-(phcnylacctyl)-Gly-Val would have been identical under the achiral conditions of the study. 

PA = 226 kcal moP ), the predominant formation (6.4 to 1) of the (7 ,5 )-di-2-butyl ether over the (R,R) and (5, 5 )-forms is attributed to a simple backside displacement in the proton-bound adduct of the starting 2-butanol enantiomer with inversion of configuration of the reaction site and loss of a molecule of water. When tri-n-propylamine is replaced by the less basic NH3 (PA = 196 kcal moF ), fast neutralization of the proton-bound dimers of the starting 2-butanol is prevented and, therefore, they can grow, producing aggregates that resemble solution microenvironments in which SnI pathways may be accessible as well. In them or in their primary substituted derivatives, consecutive nucleophilic displacements may take place. As a consequence, the stereospecificity of the process is lost and the [(R,S)-di-2-butyl ether]/[(7 ,7 )- and (5, 5 )-di-2-butyl ethers] ratio falls down to 1.2. In this case. 

Although the cinchonan carbamate-based CSPs are of primary interest for the separation of chiral acids, it needs to be stressed that the scope of application is, however, not restricted to chiral acids. A few reports in the literature deal with the separation of the enantiomers of neutral and weakly basic chiral compounds, respectively, on quinine carbamate-type CSPs [50-54]. Both RP and NP modes may be applicable. 

The separation mechanism is based on stereoselective ion-pair formation of oppositely charged cationic selector and anionic solutes, which leads to a difference of net migration velocities of the both enantiomers in the electric field. Thus, the basic cinchona alkaloid derivative is added as chiral counterion to the BGE. Under the chosen acidic conditions of the BGE, the positively charged counterion associates with the acidic chiral analytes usually with 1 1 stoichiometry to form electrically neutral ion-pairs, which do not show self-electrophoretic mobility but... 

However, a separation of the enantiomers will only be achieved if (i) the complexes have different equilibrium constants so that the two enantiomers have a different average mobility, (ii) the free and the complexed enantiomers have different mobilities and (hi) the exchange between the free and the complexed enantiomers is rapid. As a direct consequence of the second requirement, neutral enantiomers are not resolvable with neutral chiral selectors. 

When using PFT with a neutral selector, it is quite difficult to avoid any entrance of the chiral selector into the ionization source, particularly at a high pH, where EOF is important. The use of BGE at low pH and/or coated capillary to minimize EOF is therefore mandatory. However, the coaxial sheath gas, which generally assists the ionization process, leads to an aspirating phenomenon of the chiral selector in the MS direction. Javerfalk et al. were the first to apply PFT with a neutral methyl-/i-CD for the separation of racemic bupivacaine and ropivacaine with a polyacrylamide-coated capillary and an acidic pH buffer (pH 3). Cherkaoui et al. employed another neutral CD (HP-/1-CD) with a PVA-coated capillary for the analysis of amphetamines and their derivatives. To prevent a detrimental aspiration effect, analyses were carried out without nebulization pressure. Numerous other studies presented excellent results such as the enantioselective separation of adrenoreceptor antagonist drugs using tandem mass spectrometry (MS/MS) the separation of clenbuterol enantiomers after solid-phase extraction (SPE) of plasma samples or the use of CD dual system for the simultaneous chiral determination of amphetamine, methamphetamine, dimethamphetamine, and p-hydroxymethamphetamine in urine. 

In the neutral BIPHEP-Pt complex, the axial chirality of BIPHEP moiety is controlled by chiral diol BINOL as shown in Scheme 8.29. However, the diastereo-meric purity is not high enough (95 5). Therefore, recrystallization is essential to obtain the single BIPHEP-Pt diastereomer and subsequent enantiomer. It has thus been required that complete chirality control of both neutral and cationic BIPHEP-Pt complexes without recrystallization and its application to asymmetric Lewis acid catalysis (Scheme 8.32)." Interestingly, both enantiopure (5)- and (7 )-BIPHEP-Pt complexes can be obtained quantitatively through the... 

Y Tanaka, M Yanagawa, S Terabe. Separation of neutral and basic enantiomers by cyclodextrin electrokinetic chromatography using anionic cyclodextrin derivatives as chiral pseudo-stationary phases. J High Res Chromatogr 19 421-433, 1996. 

H Nishi. Enantiomer separation of basic drugs by capillary electrophoresis using ionic and neutral polysaccharides as chiral selectors. J Chromatogr A 735 345-351, 1996. 

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