The utility of peptidomimetics as enzyme inhibitors is well documented in the pharmaceutical field.  HIV protease inhibitors have been particularly successful, with ten marketed peptidomimetics.  Their success has led to activity in other areas, including inhibition of other viral enzymes such as the Hepatitis C protease HCV NS3-4a. Peptidomimetics are also in development as inhibitors of beta-secretase (BACE) for the treatment of Alzheimer's disease.  However, relatively few syntheses of semi-rigid cyclopropyl analogs have been reported. A three-step synthesis of a core cyclopropyl-containing peptidomimetic has been developed in our laboratory: Grignard addition to amino acid Weinreb amides provides enones that are substrates for the cyclopropanation. Extension of the core cyclopropyl products to provide compounds that may be expected to have activity as either BACE inhibitors or HCV NS3-4a protease inhibitors will be presented here.

Synthesis of cyclopropyl peptidomimetics as potential BACE and HCV NS3-4a protease inhibitors

243rd National Meeting (2012)

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