A Single Enantiomer Preparation of ProzacŪ and a Novel Synthesis of Amides
Aaron Pace, Regan Jones, Charles Nguyen, Judy Tang
Faculty Advisor: D. Deardorff

     Several modern-day pharmaceuticals consist of molecules that are chiral. These molecules are of special importance because they are composed of enantiomers. Enantiomers are nearly identical molecules that are non-superimposable mirror images of each other. Interestingly enough, enantiomeric pairs often have different effects within the body. We are working on two ideas, the first to show that a drug such as ProzacŪ can be made using our process, and the second, to increase the number of functional groups on our enantiopure molecules.
     The anti-depressant ProzacŪ is a chiral drug that is composed of two enantiomers. This compound is currently prescribed as a racemate, meaning that it consists of equal amounts of the two enantiomeric forms. Although each enantiomer has anti-depressant affects within the body, it is found that the drugs (S)-enantiomer has anti-migraine properties in addition to its anti-depressant. Unfortunately, these affects are masked when the drug is taken in its racemic form. Our research proposes a method of synthesizing the pure (S)-enantiomer of ProzacŪ in order to unleash the molecules anti-migraine affects. In order to synthesize the molecule, a cyano group must be converted to an amide. Currently there are few ways that work to do such a conversion. We have developed mild reaction conditions to create the change and leave the stereochemistry of the molecule unchanged.

Support provided by: National Science Foundation and the Howard Hughes Medical Institute