Drugs, chiral molecules

High performance capillary electrophoresis in its current form is a new technique. Its feasibility has been proven by the analysis and separation of small ions, drugs, chiral molecules, polymers, and biopolymers.93 We are learning more every day about the small tricks of the trade of the technique, and the efficiency and reproducibility of the methods are improving. 

Chiral Auxiliary A chiral auxiliary is an intermediate formed by the attachment of a pure enantiomer to an achiral substrate. The attachment, called a chiral auxiliary, restricts the approach of reactants to react in specihc ways to produce the chiral molecule. The antibacterial drug aztreonam is synthesized using the chiral auxiliary method. 

The last example reflects in a modest way the importance of the study of stereoisomerism. Biological conversions represent a glorious array of diastereomeric reactions and interactions a given chiral amino acid is metabolized but its enantiomer is not a certain complex drug (often a chiral molecule) alleviates pain but its enantiomer is inactive and subdc changes in structure alter a given chiral compound s action completely in the human body. 

A racemic mixture contains equal amounts of the (+) enantiomer and the (-) enantiomer and has the designation (+/-). Racemic mixtures are not optically active, because the rotation of the dextrorotatory enantiomer cancels out the rotation of the levorotatory enantiomer. Synthesis or isolation of a single enantiomer in the laboratory is a challenging task, and most syntheses of chiral molecules result in a racemic mixture containing both enantiomers. The Food and Drug Administration (FDA) policy statement drafted in 1992 and updated in 20053 requires pharmaceutical companies to characterize the properties of single enantiomers, and this adds difficulty, time, and expense to development of new medicines. 

Enzymes often prove to be the catalyst of choice for numerous transformations, and their prowess is particularly noteworthy for the synthesis of chiral molecules. The ability of biocatalysts to impart chirality through conversion of prochiral molecules or by transformation of only one stereoisomer of a racemic mixture stems from the inherent chirality of enzymes. As noted in the introduction to this book (Chapter 1), the chiral drug market is increasing, partly as a result of the need to produce single enantiomers as advocated by the U.S. Food and Drag Administration.1 The ability to extend the patent life of a drug through a racemic switch also plays a role in this increase. An example of a racemic switch is Astra Zeneca s Esomeprazole, a proton pump inhibitor (see Chapter 31).2... 

Most of the molecules we find in nature are chiral—a complicated molecule is much more likely not to have a plane of symmetry than to have one. Nearly all of these chiral molecules in living systems are found not as racemic mixtures, but as single enantiomers. This fact has profound implications, for example, in the chemistry of drug design, and we will come back to it later. 

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