Enantiomers, specificity, range

From the study with variable concentration of the amine, the yellow solution of (RRRR)-53 in chloroform remains unaltered by addition of the amine in a range of concentrations, 4.8 xlO-7 to 1.2xlO 6M, whereas the solution of (SSSS)-53 reveals a color change from yellow to reddish violet with the same concentration of the amine. In other words, enantiomer selective complexation and enantiomer specific coloration were realized by this finding. 

If the enantiomer specificity is expressed by the separation factor a, [the ratio of the distribution coefficients between solution and polymer of L- andD-form] values of cx in this and similar cases range from 1.20 to 3.66 depending upon the equilibration conditions and polymer structure. The highest a-value obtained to date was 3.66. In this case, the simple batch procedure gives an enrichment of 13% of the L-form in the filtrate and 40% of the D-form on the polymer (23). 

Medici et al. have used a combined sequential oxidation-reduction to access a range of imsaturated secondary alcohols from their racemates [7] (Scheme 1). Here the S-alcohol 2 is oxidized by B. stereothermophilus which is displaying Prelog specificity leaving the l -enantiomer untouched. The other microorganism, Y. lipolytica contains an anti-Prelog dehydrogenase which is therefore able to reduce the ketone 1 to the l -alcohol 2. Thus the combination of the two steps effects a net deracemization of substrate 2. 

Identifying pharmaceuticals, whether APIs or excipients used to manufacture products, and the end products themselves is among the routine tests needed to control pharmaceutical manufacturing processes. Pharmacopoeias have compiled a wide range of analytical methods for the identification of pharmaceutical APIs and usually several tests for a product are recommended. The process can be labor-intensive and time-consuming with these conventional methods. This has raised the need for alternative, faster methods also ensuring reliable identification. Of the seven spectroscopic techniques reviewed in this book, IR and Raman spectroscopy are suitable for the unequivocal identification of pharmaceuticals as their spectra are compound-specific no two compounds other than pairs of enantiomers or oligomers possess the same IR... 

Enantiomers can be distinguished by their rotation of plane-polarized light at a specific wavelength, or over a range of wavelengths (optical rotatory dispersion, ORD), as well as by the difference in absorption of right and left circularly polarized light (circular dichroism. Cotton effect, CD). 

In keeping with the earlier format we aim to provide the readership with sufficient practical details for the preparation and successful use of the relevant catalyst. Coupled with these specific examples, a selection of the products that may be obtained by a particular technology will be reviewed. In the different volumes of this new series we will feature catalysts for oxidation and reduction reactions, hydrolysis protocols and catalytic systems for carbon-carbon bond formation inter alia. Many of the catalysts featured will be chiral, given the present day interest in the preparation of single-enantiomer fine chemicals. When appropriate, a catalyst type that is capable of a wide range of transformations will be featured. In these volumes the amount of practical data that is described will be proportionately less, and attention will be focused on the past uses of the system and its future potential. 

Values for the enantiomer ratio found in natural products can range from 0% to 100%. If the enantiomeric purity is 100%, care must be taken to determine which isomer is present by comparison of retention times with a known standard. Samples from different geographic or growing regions may show some variation in the ratio of a specific compound, while others will not deviate from a known value. 

It is essential that the specific rotation of the product and the pure enantiomer be measured in the same solvent, at the same wavelength and temperature, and at a similar concentration if possible both measurements should be made at the same time. Optical yields in enzymic reactions carried out under laboratory conditions approach 100 per cent an asymmetric chemical synthesis may be regarded as promising if the optical yield ranges upwards from 20 per cent. 

A rapid, sensitive, and enantioselective LC-MS-MS method using deuterium-labeled IS was developed and evaluated for the simultaneous quantitative determination of donepezil enantiomers in human plasma without interconversion during clean-up process and measurement [37]. The use of an avidin column allowed the separation of donepezil enantiomers, which were specifically detected by MS-MS without interference from its metabolites and plasma constituents. Evaluation of this assay method shows that samples can be assayed with acceptable accuracy and precision within the range from 0.0206 to 51.6 ng/ml for both R-donepezil and S-donepezil. This analytical method was applied to the simultaneous quantitation of donepezil enantiomers in human plasma. 

Schramm et al. [48] described a gas chromatographic method for determination of vigabatrin enantiomers in plasma. The method used a double derivatization step on a megabore Chirasil-Val capillary column and thermionic specific detection. The calibration graphs for the R-(-) and (S)-(+)-enantiomers were linear over the concentration range of 1.0-200 and 0.5-100 fig/ml, respectively. The assay was suitable for pharmacokinetic studies and routine therapeutic drug monitoring in humans. 

A substrate binds an enzyme at the active site. Substrate-enzyme binding is based on weak intermolecular attractions contact forces, dipole forces, and hydrogen bonding. Steric effects also play an important role because the substrate must physically fit into the active site. Some enzymes have confined active sites, while others are open and accessible. A restricted active site can lead to high selectivity for a specific substrate. Low specificity can be advantageous for some enzymes, particularly metabolic and digestive enzymes that need to process a broad range of compounds with a variety of structures. Because enzymes are composed of chiral amino acids, enzymes interact differently with stereoisomers, whether diastereomers or enantiomers. 

Die specificity of the dopamine receptor was further studied with a series of dopaminergic antagonists of well known pharmacological activity. The 30-40% inhibitory effect of 10 nM dopamine was completely reversed by the addition of increasing concentrations of the potent neuroleptics (+)butaclamol (Kp = 1.5 nM) and (-)sulpiride (Kp = 0.5 nM) while their pharmacologically weak enantiomers (-)butaclamol and (+)sulpiride were 86 and 167 times less potent, respectively. The neuroleptics spiroperidol, thioproperazine, domperidone, haloperidol, fluphenazine and pimozide completely reversed the inhibitory effect of dopamine at low Kp values ranging from 0.02 to 0.8 nM (41). 

Chiral ketone 51 (derived from glucose, and therefore available as either enantiomer) was introduced in 2000 as an asymmetric epoxidation catalyst specifically for r-olefins, giving good results for a range of unsubstituted cycloalk-enes (Table 5, entries 6-12) <2000JA11551, 2002JOC2435>. 

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