Chirality: a blueprint for the future
by
Burke D, Henderson DJ.
Department of Anaesthesia,
St John's Hospital at Howden,
Livingston, UK.
Br J Anaesth. 2002 Apr;88(4):563-76

ABSTRACT

The chirality that is inherent in the enzyme systems of living organisms results in an abundance of enantiopure organic molecules in the living world. In addition to the optical properties first noticed by Pasteur, stereospecific interactions at recognition sites result in differences in both biological and toxicological effects. This fact underlies the continuing growth in chiral chemistry, rooted as it is in fundamental biochemistry. The pharmaceutical industry has undergone a strategic shift and embraced the wide spectrum of asymmetrical synthetic methods now available. The use of these processes in developmental synthesis and large-scale manufacturing has provided new challenges in drug discovery, motivated by a desire to improve industrial efficacy and decrease the time from the conception of a new drug to the market. The economic impact of the industrial production of chiral drugs is now huge--more than 50% of the 500 top-selling drugs were single-enantiomers in 1997. Sales have continued to increase by more than 20% for the past 6 yr and worldwide annual sales of enantiomeric drugs exceeded US$100 billion for the first time in the year 2000, chiral drugs representing close to one-third of all sales worldwide. While some 'chiral switches' may be of less apparent benefit, or indeed detrimental in some cases, encouragement by the regulatory agencies and the ability to extend the life cycle of a drug coming off patent promotes the trend. However, it may turn out to be the ability to provide chiral templates, and thereby attack the key targets of selectivity and specificity, that will lead to the greatest benefits. Research into new chemical entities that can interact specifically with enzyme families may potentially lead to new therapies for complex disease processes. As Richards has stated, the approach is designed to create a made to measure product, rather than one off the peg.

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