Drugs, People and Mirrors: A New Wave in Pharmaceuticals

Abstract

Most people assume when taking a drug that it is pure and safe; most of the time they are correct, but not always. Many drugs consist of a one to one blend of enantiomers (racemic mixture). Enantiomers exist in pairs, differing only in their orientation in space. Enantiomers are mirror-images but are not superimposable; this is chirality. Right and left hands are representative examples of chirality. They look similar and reflect each other's image, but they cannot be superimposed. Conversly, achiral objects, like pencils, have superimposable mirror images. Chirality only manifests itself when two chiral objects interact. Thus, when a chiral hand holds an achiral ball, it feels the same whether that hand is a left or right. When one attempts to put a left glove on a left hand, it feels different from a right glove on a left hand. By extension, a right-handed molecule is expected to interact differently with each enantiomer of an enantiomeric pair. Human biochemical enzymes evolved asymmetrically, with only one enantiomer present. Thus each enantiomer of a racemic drug is expected to interact differently with biological enzymes; outside research has substantiated this. A new wave in pharmaceuticals is aimed at creating single-enantiomer drugs. Specifically, my project is to develop facile syntheses of enantiopure drug analogues. These syntheses involve the enzyme oxynitrilase, which creates the enantiopure center. A Pd(0) catalyst allows us to shift the center of chirality, which allows ultimate control over the regiochemistry of our molecules.