Rob Broadrup

My research has focused on the development of enzyme inhibitors in two distinct areas. Firstly I have been working on an efficient method to synthesize alpha-aminophosphonic acids, molecules that are analogues of the intermediate formed in enzyme-catalyzed acyl substitution reactions. Such alpha-aminophosphonic acids have been incorporated into peptidomimetics and used as enzyme inhibitors. My research has concentrated on the chiral, non-racemic synthesis of these molecules involving the following key steps: an asymmetric, oxazolidinone auxiliary-directed enolate alkylation and a Curtius rearrangement. Secondly I have pursued the synthesis of 4- through 8-membered lactam-containing monocycles with the Mitsunobu reaction as the key step. We hope to demonstrate that these molecules can by themselves, or as elaborated into larger units, function as peptidomimetic inhibitors of serine or cysteine proteases through a mechanism whereby the lactam moiety acylates the enzymeís active site nucleophile.