|
Studies
on the Enantioselective Synthesis of Cymbalta™ The enantioselective synthesis of Cymbalta™ is reported. Cymbalta™ is a serotonin reuptake inhibitor intended for individuals with major depressive disorder (MDD), generalized anxiety disorder (GAD), and pain related to diabetic neuropathy. Cymbalta™ is unique because it can provide protection from especially severe symptoms where other drugs cannot ( for instance Prozac™). Consequently, Cymbalta™ is an excellent synthetic target. Our synthetic route of Cymbalta™ first establishes asymmetry by use of oxynitrilase, an enzyme isolated from raw almonds which is used to establish a chiral center in crotonaldehyde to yield (R)-cyanohydrin. This (R) asymmetry is maintained while adding functional groups to the molecular backbone. Reactions with academic importance are the addition of thiophene via Grubbs metathesis and alpha-naphthol via palladium catalysis. The three reactions mentioned above have successfully yielded the desired product, which proves our synthetic route to be a strong candidate for the enantioselective production of Cymbalta. Support provided by: Howard Hughes Medical Institute Undergraduate Science Education Grant |
