Amides, enantiomeric separation

Adsorption surface, SFC, solvent Interactions, 1>>9 Air monitors. Industrial chromatography, 200 Alditol acetates, chromatogram, 32f Alkyl groups, bonded, HPLC development, 82,83 Amides, enantiomeric, separation, >l3,>l>lf Amine compounds, RPLC, 8>l Amino acids HPLC, 86,87f Ion exchange, 81 ligand exchange, >>... 

Macaudiere et al. first reported the enantiomeric separation of racemic phosphine oxides and amides on native cyclodextrin-based CSPs under subcritical conditions [53]. The separations obtained were indicative of inclusion complexation. When the CO,-methanol eluent used in SFC was replaced with hexane-ethanol in LC, reduced selectivity was observed. The authors proposed that the smaller size of the CO, molecule made it less likely than hexane to compete with the analyte for the cyclodextrin cavity. 

Owing to the high thermal and long-term stability, amide phases bonded to polysiloxane are regarded as sensitive materials for the sensoric approach to enantiomeric separation. An important factor for the resolution of the stationary material is the number of dimethylpolysiloxane units between the chiral moieties. More than 200 different amide phases have been synthesised and applied for the discrimination of amino acids, lactate esters and many other substances [10]. 

Vogtle, F., Hiinten, A., Vogel, E., Buschbeck, S., Safarowsky, O., Recker, J., Parham, A, Knott, M., Muller, W.M., Muller, U., Okamoto, Y., Kubota, T., Lindner, W., Francotte, E., Grimme, S. Novel amide-based knots complete enantiomeric separation, chiroptical properties, and absolute configuration, Angew. Chem. 113 (2001), 2534-2537 Angew. Chem. Int. Ed. 40 (2001), 2468-2471. 

Enantiomeric separation of a wide range of secondary amides using binary mobile phases... 

Active research on the development of further cinchonan-based anion exchangers is in progress. In this context we have recently shown that also O -modified CSPs (with other than methoxy substituents at Ri. see Fig. 9.32) 90], carbamoylated C -dimeric CSPs 1390], and CX -hydrazide CSPs [391] as well as C -urea and Cy-amide-modified cinchonan-derived CSPs possess a high potential for enantiomeric separations of acidic SAs. 

For characterization and exploitation of the diamide-phase system, a chiral diamide, e,g., (Ill) was examined as a modifier in the mobile phase (solvent) in conjunction with a non-bonded (bare) silica. Such a chiral carrier separated enantiomeric N-acyl-d-amino acid esters and amides with separation factors comparable to those for bonded stationary phase systems. The resolution can be as cribed to diastereomeric complexation through amide-amide hydrogen bonding between the amide additive and enantiomeric solute molecules in the carrier solvent, followed by separation of the diastereomeric complexes by the (achiral) silica phase. This process should be applicable as widely as that involving chiral diamide-bonded stationary phase systems. 

Van Overbeke, A. Baeyens, W. Van den Bossche, W. Dewaele, C. Enantiomeric separation of amide derivatives of some 2-arylpropionic acids by HPLC on a cellulose-based chiral stationary phase. J.Pharm.Biomed.Anai, 1994, 12, 911-916 [chiral derivatization also, flurbiprofen, ketoprofen, tia-profenic acid]... 

Remelli et al. (168) described a selector based on histidine. With this chiral selector L-hr-n-decylhistidine (Fig. 5(c)) the simultaneous enantiomeric separation of D,L-tiyptophan and D,L-phe-nylalanine was successfully performed on hydrophobic layers with MeOH-acetonitrile-THF-water (7.3 5.9 33.9 52.9, v/v/v/v) as eluent. Sinibaldi et al. (165) resolved D,L-dansyl amino acids on reversed phase TLC plates pretreated with a copper -complex of poly-L-phenylalanine amide (Fig. 5 (d)). The polymeric ligand was synthesized by the reaction of optically active amide with ethylene glycol diglycyl ether. The method makes use of a sophisticated liquid chroinatogr q)h for obtaining the desired polymer fraction which is subsequently used for the LEC, and this might limit the application of the separation procedure. However, a simple method is performed by Bhushan et al. (169). Here L-proline was used as a chiral selector on normal phase silica gel (169) and amino acids were resolved with the eluent systems n-butanol-acetonitrile-water (6 2 3, vWv), chloroform-meth-anol-propionic acid (15 6 4, v/v/v) and acetonitrile-methanol-water (2 2 1, v/v/v). 

Novel Amide-Based Molecular Knots Complete Enantiomeric Separation, Chir-optical Properties and Absolute Configuration. 

In 1984, a new reagent, l- luoro-2,4-dinitrophenyl-5-L-alanine amide (FDAA), was reported by Marfey for the enantiomeric separation of amino acids [37]. FDAA contains the enantiomerically pine L-alanine moiety in the reagent and reacts with amino acids to form diastereomers (Figure 6.5). As of now, many Marfey reagent analogs have been reported... 

Fig. 1 GC chromatogram showing the enantiomeric separation of 2-phenethyi aicohoi, 1-phenyi-1-butanol and trani-l,2-cyclohexenediol with a fused-silicacapiiiary coiumn coated with (l.S,2R)-(+)-iVA -dimethylephedtinium bis(trifluoromethylsuifonyi)amide (4). Adapted from [40]...

The highly ordered cyclic TS of the D-A reaction permits design of diastereo-or enantioselective reactions. (See Section 2.4 of Part A to review the principles of diastereoselectivity and enantioselectivity.) One way to achieve this is to install a chiral auxiliary.80 The cycloaddition proceeds to give two diastereomeric products that can be separated and purified. Because of the lower temperature required and the greater stereoselectivity observed in Lewis acid-catalyzed reactions, the best diastereoselectivity is observed in catalyzed reactions. Several chiral auxiliaries that are capable of high levels of diastereoselectivity have been developed. Chiral esters and amides of acrylic acid are particularly useful because the auxiliary can be recovered by hydrolysis of the purified adduct to give the enantiomerically pure carboxylic acid. Early examples involved acryloyl esters of chiral alcohols, including lactates and mandelates. Esters of the lactone of 2,4-dihydroxy-3,3-dimethylbutanoic acid (pantolactone) have also proven useful. 

Unusual amino acids include a class of unnatural a-amino acids such as phenylalanine, tyrosine, alanine, tryptophan, and glycine analogs, and f)-amino acid analogs containing 1,2,3,4-tetrahydroisoquinoline, tetraline, l,2,3,4-tetrahydro-2-carboline, cyclopentane, cyclohexane, cyclohexene, bicyclo[2.2.1]heptane or heptene skeletons. Different selectors were exploited for the separation of unusual amino acids, most of the production being made by Peter and coworkers teicoplanin [41, 56, 84, 90, 93, 124, 141-144], ristocetin A [33, 94, 145, 146], and TAG [56, 147]. Enantiomeric and diastereomeric separations of cyclic -substituted a-amino acids were reported by other authors on a teicoplanin CSP [88, 89], Ester and amide derivatives of tryptophan and phenylalanine were recently analyzed on a Me-TAG CSP [58],... 

Chromatographic separatum of enantiomersThe carbamate, ureido, and amide derivatives obtained without racemization from enantiomeric amines, alcohols, and carboxylic acids, respectively (equations T III), with this isocyanate are stable for months and are suitable for gas chromatographic separation using a polymeric chiral stationary phase (derived, for example, from L-valine-(S)-a-phenylethylamide). This methodology permits separation of chiral a- and /1-hydroxy acids and also N-mclhylnmino acids. 

In 1998, Machida et al. [45] and Hyun et al. [46] developed a new CCE-based CSP (covalently bonded to silica gel see Sect. 8.2). This CSP was used successfully for the chiral resolution of certain racemic compounds using a variety of mobile phases. The most important applications of this CSP are for the resolution of amino acids, amino esters, amino alcohols, amines, amides, quinolone antibacterials, and other drugs having primary amino groups [46-51,64,65]. The typical chromatograms of the chiral resolution of amino acids on (+)-(18-crown-6)-2,3,ll,12-tetracarboxylic acid CSP are shown in Figure 4. The enantiomeric resolution of the racemic compound on CCE-based CSPs are listed in Table 2. There is no report available on the chiral separations at the preparative scale using these CSPs. 

The use of a cationic aza-Cope rearrangement in concert with a Mannich cyclization has also been applied to the total synthesis of enantiomerically pure (—)-crinine (359) (205). In the event, nucleophilic opening of cyclopentenoxide with the aluminum amide that was formed on reaction of (/ )-a-methylbenzyl-amine and trimethylaluminum gave the amino alcohol 485 together with its (15,25) diastereomer. Although there was essentially no asymmetric induction in this process, the diastereomeric amino alcohols were readily separated by chromatography, and the overall procedure therefore constitutes an efficient means for the preparation of enantiomerically pure 2-amino alcohols from epoxides. When the hydrochloride salt derived from 485 was treated with paraformaldehyde and potassium cyanide, the amino nitrile 486 was formed. Subsequent Swem oxida-... 

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