Purity, enantiomeric discrimination

Other nuclei besides H or have been used to monitor enantiomeric discrimination with chiral lanthanide chelates. This includes the NMR spectra of chiral 2-thiabicyclo[4.3.0]nonane 2,2-dioxides (14) and 8,8-dioxides (15) with Pr(hfc)3 . The Si NMR spectrum of a-C-silylated amines and alcohols (38) in the presence of Eu(tfc)3 was used to monitor the optical purity of these compounds . A refocused-decoupled INEPT (insensitive nuclei enhanced by polarization transfer) pulse sequence was used to circumvent the long spin-lattice relaxation times of the silicon. 

The analysis of isothiouronium salts, which are conveniently formed by reacting alkyl halides with thiourea, provide a way to study alkyl halides . The H NMR spectrum of s-butylisothiouronium chloride and bromide exhibited enantiomeric discrimination in the presence of [Eu(tfc)3(fod)] The enantiomeric purity of several alkyl methyl phenyl sulfonium ions (73) under conditions of slow inversion was determined using either [Eu(tfc)3(fod)] or [Eu(tfc)4] It was possible to study the inversion barrier by variable-temperature studies in the presence of the shift reagent. 

In all cases esters with an enantiomeric purity never exceeding 5% were obtained, thus indicating that enantiomeric discrimination is very poor under the adopted conditions. In spite of that, indications have been achieved on the coexistence of the two proposed... 

The resonances of nuclei that are less coupled such as singlets or doublets are often easier to monitor for the presence of enantiomeric discrimination than highly coupled, complex multiplets. However, with the high-field spectrometers available to many investigators today, a complex mul-tiplet that is free of interference with other resonances can often be used for determining enantiomeric purity or assigning absolute configuration even if there is only partial discrimination. 

The enantiomeric purity of carboxylic acids with remotely disposed chiral centers can be analyzed using 2-(anthracene-2,3-dicarboximido)cyclohexanol 36. Similar to the derivative with a carboxylic acid moiety on the cyclohexane ring 10 described earlier for the analysis of alcohols, the ester derivative of carboxylic acids with 36 positions the carbon chain of the substrate over the anthryl ring. Carboxylic acids with the stereocenter at C12 still show enantiomeric discrimination in the derivative with 36. ... 

Ketoconazole 68 is a potent, orally active, broad-spectrum antifungal agent. It is marketed as a racemic mixture of the cis-(2S,4R)- and c/5 -(2R,45()-enantiomers. A method for determining the enantiomeric purity of 68 in deuterium oxide using (3-cyclodextrin has been developed. Enantiomeric discrimination is observed in many resonances in the H and NMR spectrum. (+)-L-tartaric acid is added to the solution to form a salt with 68 that facilitates its solubility in deuterium oxide. 

Lanthanide tris-diketonates have been used extensively for the analysis of enantiomeric purity of pharmaceuticals. In one example, the utility of lanthanide chelates of tfc, hfc, and Eu(dcm)3 at causing enantiomeric discrimination in the H NMR spectra of psychostimulant drug amphetamine 86 was compared. Spectra were recorded in chloroform-considerably more effective than the other chelates at causing enantiomeric discrimination in the NMR spectrum. In forensic science, analyses of enantiomeric purity are often useful in helping to identify the source of the material. ... 

Enzymic discriminations of enantiopic groups of weso-compounds have been widely exploited in asymmetric synthesis. Ohno and co-workers reported a total synthesis of L- and D-ribose, showdomycin and cordycepin based on the optically active half-esters 56 and 57, which were obtained enzymatically (Pig Liver Esterase PLE) from the corresponding mcso-diesters 54 and 55, respectively, derived from the Diels-Alder adduct 53 of furan to dimethyl acetylenedicar-boxylate. The diesters 58 - 60 were also found to be good substrates for PLE leading to the corresponding half-esters 61 - 63 with high enantiomeric purities. ... 

For instance, when a-[2H]-styrene is hydroformylated with the Rh/(—)-DIOP catalytic system, the two reaction products obtained have almost identical optical purity and opposite absolute configuration (Fig. 2)51). Therefore, in this case, the enantiomeric excess measured indicates both the type (the re-re enantioface reacts preferentially) and extent of enantioface discrimination ( 15%) occurring during the reaction. 

The first task before beginning stress-testing studies is to gather all the relevant information about the compound. Information such as molecular structure, solubility, pA (s), known chemical instability, hygroscopicity, enantiomeric purity, etc. is important. In addition, previously established analytical methods may provide a starting point for development of more discriminating methods required for the separation of the complex mixtures which may result from stress degradation. 

Biological Discrimination of Enantiomers 189 5-6 Racemic Mixtures 191 5-7 Enantiomeric Excess and Optical Purity 192 5-8 Chirality of Conformationally Mobile Systems 193 5-9 Chiral Compounds without Asymmetric Atoms 195 5-10 Fischer Projections 197... 

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