Enantiomers biological properties

An article entitled When Drug Molecules Look in the Mirror in the June 1996 is sue of the Journal of Chemi ca/fdc/cat/on (pp 481-484) describes numerous exam pies of common drugs in which the two enantiomers have different biological properties... 

In common with the naturally occurring carbapenem thienamycin (2), the introduction of the /n j -6-[l-(R)-hydroxyethyi] group had a profound effect on the biological properties of the penems. This, together with an indication from an early study (93) that, as with other P-lactams, the 5(R)-enantiomer was solely responsible for antibacterial activity, provided impetus for the development of methods for the synthesis of chiral penems. 

Enantiomeric separations have become increasingly important, especially in the pharmaceutical and agricultural industries as optical isomers often possess different biological properties. The analysis and preparation of a pure enantiomer usually involves its resolution from the antipode. Among all the chiral separation techniques, HPLC has proven to be the most convenient, reproducible and widely applicable method. Most of the HPLC methods employ a chiral selector as the chiral stationary phase (CSP). 

Although the different enantiomers of a chiral molecule have the same physical properties, they usually have different biological properties. For example, the (+) enantiomer of limonene has the odor of oranges, but the (-) enantiomer has the odor of pine trees. 

Enantiomers are characterized as nonsuperimposable mirror images. Enantiomers are said to be chiral (note that some diastereomers may be chiral as well). In the context of the same bonding pattern or connectivity, which atoms are bonded to which, enantiomers have handedness and are related to each other as the right hand is related to the left hand. In the specific example we saw earlier, the carbon atom is linked to four different atoms. Such molecules have non-superimposable mirror images. Stereoisomerism occurs in some molecules that do not have such a carbon atom but these cases are more exotic than we need to worry about here. Stereoisomers frequently have different, and sometimes strikingly different, biological properties, exemplified by the thalidomide case. 

The geometric isomers 464 and 467 of 5(47/)-oxazolones prepared from acetophenones can be separated. Alternatively, the mixture can be isomerized under the appropriate reaction conditions to obtain the pure of (Z) or ) isomer. Each isomer can be converted to a pair of enantiomers 466 and 469 (only one enantiomer shown) (Scheme 7.152). The p-methyl phenylalanine analogues thus obtained are constrained phenylalanines and the effect of incorporation of a p-MePhe or p-MeTyr residue on the biological properties of H-Tyr-Tic-Phe-Phe-NH2 (TIPP, where Tic = l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) a delta opioid receptor antagonist, has been studied. ... 

Differences in the biological properties of the enantiomers have also been reported for other azole products that possess one or more chiral centers in the molecule. These few results clearly show that, as in many other biologically active classes of compounds, the... 

Unique physicochemical (e.g., polymorphic forms, enantiomers) and biological properties... 

---