Enantiomeric purity analysis

An interesting feature of this study is the enantiomeric purity analysis of the products. By converting the amine functionality of the pyrrolidine to a 3,5-dinitrobenzamide, the substrate can be analyzed by chiral HPLC. To date, the 3,5-dinitrobenzamide of 2-substituted pyrrolidines that the submitters have prepared have beer baseline-resolved by the Pirkle S-N1 N-Naphthylleucine column. This approach obviates the need for MPTA-derivativization which has been previously employed in enantiomeric purity determinations.3 5... 

Authenticity evaluation has recently received increased attention in a number of industries. The complex mixtures involved often require very high resolution analyses and, in the case of determining the authenticity of natural products, very accurate determination of enantiomeric purity. Juchelka et al. have described a method for the authenticity determination of natural products which uses a combination of enantioselective multidimensional gas chromatography with isotope ratio mass spectrometry (28). In isotope ratio mass spectrometry, combustion analysis is combined with mass spectrometry, and the ratio of the analyte is measured versus a... 

The development of a single enantiomer as a new active substance should be described in the same manner as for any other new chemical entity. Studies should be carried out with the single enantiomer, but if development began with the race-mate then these studies may also be taken into account. Chiral conversion should be considered early on so that enantiospecific bioanalytical methods may be developed. These methods should be described in chemistry and pharmacy part of the dossier. If the opposite enantiomer is formed in vivo, then it should be evaluated in the same way as other metabolites. For endogenous human chiral compounds, enantiospecific analysis may not be necessary. The enantiomeric purity of the active ingredient used in preclinical and clinical studies should be stated. 

Sl-a-Phenylethylaminc (2a 94% ee) and (.S)-2-heptylamine (2b 82% ec) were synthesized from enantiomerically pure nitrones 1 a and 1 b (33-39% overall yield). The enantiomeric purity of the amines was determined by HPLC analysis of their 3,5-dinitrobenzamidines on a D-naphthyl alanine column,... 

The complex 65 was synthesized by reaction of the imidazolinium salt with the precursor ruthenium complex 67 (catalytically inactive) in the presence of silver carbonate (Scheme 42). The complex being air-stable and stable on silicagel was isolated in 52% yield after chromatography. The diastereomeric and enantiomeric purity of 65 was determined by HPLC analysis and found to be above 98% (de and ee). The molecular structure was determined by X-ray analysis and showed the unusual twist geometry of this complex. 

Like plasma and urine, matrixes from plant or environmental sources contain a vast diversity of components. Thus, achiral-chiral LC-LC is also useful for analysis involving samples from these sources. Stalcup et al. (1991) studied the enantiomeric purity of scopolamine extracted from Datura sanguinea in both homogenized plant leaves and commercial extracts. A reverse-phase separation on a C j g column separated the scopolamine from other alkaloid and matrix components while the enantiomeric separation (also in the reverse-phase mode) was carried out on two coupled [3-cyclodextrin columns or a single acetylated (3-cyclodextrin column. The single... 

An optically pure polyester has been synthesized by PPL-catalyzed enantioselective polymerization of bis(2,2,2-trichloroethyl) frans-3,4-epoxyadipate with 1,4-butanediol in anhydrous diethyl ether (Fig. 4) [47]. The molar ratio of the diester to the diol was adjusted to 2 1 so as to produce the (-) polymer with enantiomeric purity of > 96 %. From end group analysis, the molecular weight was calculated to be 5.3 x 103. 

The enantiomeric purity of vinylsilane (S)-3a and (R)-3c are determined to be >95% ee by 1H-NMR (400 MHz) on the derived mandelate ester, obtained by a DCC-promoted coupling to (R)-O-acetylmandelic acid, and absolute stereochemical assignment is accomplished by 1H NMR analysis of the derived (R)-O-acetyl-mandelate esters. For details of this procedure see the published method of Trost.3... 

The product of this preparation is the most enantioselective catalyst developed to date for asymmetric epoxidation of a broad range of unfunctionalized olefins.6 The procedure includes a highly efficient resolution of trans-1,2-diaminocyclohexane as well as a convenient analytical method for the determination of its enantiomeric purity. This method is general for the analysis of chiral 1,2-diamines. The Duff formylation described in Step B is a highly effective method for the preparation of 3,5-di-tert-... 

Barretta and coworkers63 reported a direct determination of the enantiomeric purity of chiral trisubstituted allenes by using permethylated cyclodextrin as a chiral solvating agent. They found that the heptakis ft-cyclodextrin TRIMEB discussed above can be successfully used as a chiral solvating agent (CSA) for the NMR determination of the enantiomeric purity of trisubstituted allenes llOa-f. An accurate analysis of the experimental conditions (molar ratio aliene/TRIMEB, temperature and solvent) required to optimize the enantioseparation has been carried out. The XH NMR spectra of TRIMEB, allenes llOa-f, and the mixtures TRIMEB/allene have been recorded at 300 MHz in CD3OD as solvent. 

This reversal of elution order is due to the changed CIP priorities, but not a result of an altered binding and chiral recognition mechanism. Moreover, in yet another study, BOC and DNP-protected a-substituted proline derivatives have been resolved into enantiomers and elution orders were determined [48], The method allowed the sensitive and accurate analysis of samples with regards to their enantiomeric purities. 

However, the revision of many naturally occurring amino acids is under progress. For limitation of other amino acids various methods such as ion chromatography, amino acid analysis, HPEC, and CZE are available and have to be tested case by case. In addition, tests for other non-amino acid related substances have to be developed. Possibly substances of different origin (production by synthesis, by fermentation, or by protein hydrolysis) may need different methods. In addition, a test for enantiomeric purity has to be included. 

The BINAP derivative of the ort/io-cyclometallated iridium catalyst has been characterized by single crystal X-ray diffraction analysis [280]. Remarkably, although the reaction sequence depends upon oxidation of either the reactant alcohol or isopropanol, the enantiomeric purity of the homoallylic alcohol product... 

Figure 3.9 Measurement of the enantiomeric purity of the pharmaceutical intermediate SB-240093 using CD-modified CE. The electropherogram shows the analysis of the chiral system suitability standard containing 0.5% w/w of the R-enantiomer. (Conditions PVA-coated fused silica capillary, 50 cm effective length, 57 cm total length, 50 pm i.d. buffer sodium phosphate [pH 7.0, 100 mM] containing 1.75 mM dimethyl-/l-CD voltage —30 kV [reversed polarity] temperature 20°C detection UV at 200 nm sample preparation 0.5 mg/ml in water DMSO (95 5, v/v) sample introduction 6 s at 35 mbar, capillary inlet at cathode.)...

Ravid U, Putievsky E, Katzir I, Chiral GC analysis of (l./ )(-b)- puiegone with high enantiomeric purity in essential oils of some Lamiaceae aromatic plants, Flavour Fragr J 9 2Q)>—2Qi7, 1994. 

The method has been extended to include chemical shift imaging, which allows even higher throughput (99). In this embodiment, a 19-capillary through-flow system enables the simultaneous analysis of 19 samples. The enantiomeric purity of 5600 samples can be determined within one day, the precision being +6%. In this... 

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