Enantiomers basic properties

In summary, Sanofi presented two superior and unexpected results, in the form of a highly significant combination of properties [associated with one enantiomer], as part of a point-by-point rebuttal of Apotex s arguments in its prima facie obviousness case. By doing so, Sanofi retained patent protection for Plavix. Superior and unexpected results can thus overcome a basic case of obviousness and confer patentability, even in the close case of an enantiomer compared to a racemate. 

The separation (resolution) of a racemic modification into its constituent enantiomers is normally achieved by converting the enantiomers in the racemate into a pair of diastereoisomers by reaction with a pure enantiomer (Figure 10.4.). Enantiomers of acids are used for racemates of bases whilst enantiomers of bases are used for racemates of acids (Table 10.1). Neutral compounds may sometimes be resolved by conversion to an acidic or basic derivative which is suitable for diastereoisomer formation. The diastereoisomers are separated using methods based on the differences in their physical properties and the pure enantiomers are regenerated from the corresponding diastereoisomers by suitable reactions. 

The kinetic method provides an alternative to equilibrium measurements for the determination of gas-phase thermochemical properties. It has been applied more and more in thermochemical data determination mainly because of its ability to measure very small energy differences and its simplicity. Indeed, it can be executed easily on any tandem mass spectrometer. Furthermore, this method is sensitive and is applicable with impure compounds. Its applications are broad, covering thermochemical properties in the gas phase such as proton affinity [46], electron affinity [47], metal ion affinity [48], ionization energy [49], acidity [50] or basicity [51], In addition to the determination of thermochemical data, the kinetic method has also been applied in structural and chemical analysis such as chiral distinctions. This method is able to distinguish enantiomers and to measure precisely enantiomeric ratios [52],... 

Stereoisomers are classified by symmetry as either enantiomers or diaste-reomers. Enantiomers have identical physical properties except for the direction of optical rotation. Diastereomers are basically stereoisomers that are not enantiomers of each other. A pair of enantiomers exists for all molecules containing a single chiral center and have the opposite configuration at each of the stereo centers. The maximum number of stereoisomers for a compound with n stereo centers is T. Diastereomers, on the other hand, have the same configuration at one of the two centers and have the opposite configuration at the other. 

As with the other protein-based CSPs, initial studies indicate a relationship between the structure of the protein and chromatographic properties of the OVM CSP (101). When the sialic acid residues, were enzymatically removed from the protein, the capadty factors (k ) of the enantiomers of an addic solute (ketoprofen) were reduced, whereas the k s of the enantiomers of a basic solute (chlorpheniramine) were un-... 

Hermansson, J. Grahn, A. Optimization of the separation of enantiomers of basic drugs. Retention mechanisms and dynamic modification of the chiral bonding properties on an Ui-acid glycoprotein column. J.Chromatogr.A, 1995, 694, 57-69... 

GC is basically a technique for analytical enantioseparations. However, micropreparative separations are also feasible using this technique. The most impressive example of the application of chiral GC for micropreparative enantioseparation of drug enantiomers is the chiral inhalation anesthetic drug, enflurane. According to recent data, the enantiomers of isoflurane may have different pharmacological properties [94]. For the isomeric compound enflurane (Fig. 3) a more intensive metabolism was established for the (ft)-(-)-enantiomer compared with the (S)-(+)-enantiomer [95]. Enflurane is a gas and therefore, the most favorable method for the enantioseparation will certainly be GC. Analytical-scale enantioseparations of this compound have been reported using various CD derivatives as CSPs [97]. The micro-... 

Enantiomers also are referred to as chiral compounds, antipodes, or enantiomorphs. When introduced into an asymmetric, or chiral, environment, such as the human body, enantiomers will display different physicochemical properties, producing significant differences in their pharmacokinetic and pharmacodynamic behavior. Such differences can result in adverse side effects or toxicity, because one or more of the isomers may exhibit significant differences in absorption (especially active transport), serum protein binding, and metabolism. With the latter, one isomer may be converted into a toxic substance or may influence the metabolism of another drug. To discuss further the influence of stereochemistry on drug action, some of the basic concepts of stereochemistry need to be reviewed. 

The kinetics of excretion are a direct consequence of the kinetics of metabolic transformations. The faster a drug is metabolized, the faster its elimination can be expected. In accordance with this assertion, rats given R,S( ), S(+), and R(-)-amphetamine, were found to excrete less (+)-p-hydroxy-amphetamine than its (-)-isomer this may be the basic explanation of the more pronounced pharmacological properties of the dextro-, compared to the levoampheta-mine. For the hypnotic agent hexobarbital, the ehmination half-life in man is about three limes longer for the more active (-l-)-isomer then for the less active ( )-isomer. This was attributed to a difference in hepatic metabolic clearance and not in volumes of distribulion or plasma binding between the enantiomers. " ... 

The responsiveness of the irradiated molecule to the CPL is more formally known as the g (or anisotropy) factor the relative difference of the extinction coefficients exhibited by an enantiopure compound to right and left CPL [49-51]. Thus, the success of the method is dependent on a basic physical property of the molecule as well as the conditions used [52, 53], meaning that, Hke aU the other processes described in this book, the appHcabihty of the method of the separation of enantiomers varies depending on the structure of the molecule under consideration and the conditions (such as solvent) that may be employed. 

Since l-amino-2-cyclohexene is basic, a chiral acid is needed. When (+)-mandelic acid is the resolving agent used, a mixture of diastereomeric salts is formed as shown. These diastereomers have different physical properties and can therefore be separated (often by recrystaUization). Treatment with base neutralizes the amine and allows it to be separated from the charged mandelate salt (typically by extraction), to give the neutral amines as pure enantiomers. 

Second-harmonic generation for nonlinear optics, ferroelectricity, and piezoelectricity are all properties that are dependent on the pre.sence, magnitude, and orientation of bulk polarity in crystals and films. Therefore, the issue of how to design a polar solid from basic principles remains a challenge that has immense potential relevance to materials science. Obviously, a polar solid is guaranteed if a pure enantiomer is used as a component of a compound. However, the presence of polarity does not in any way imply that optimal packing will occur and, further-... 

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