We propose a number of synthetic and mechanistic studies related to chorismic acid, a key intermediate in the biosynthesis of aromatic metabolites. 1. We plan to elucidate the stereochemistry of the Claisen rearrangement of chorismate to prephenate by developing a synthesis of stereospecifically labeled deuterochorismate. 2. We will synthesize a transition state analog of the rearrangement and evaluate it as an inhibitor of chorismate mutase enzymes and as a potential antibiotic. 3. We will develop total syntheses of the still-virgin intermediates in the shikimic acid pathway: shikimate-3-phosphate, 5-enolpyruvylshikimate-3-phosphate, and chorismate itself.
