Synthesis of novel cyclic protease inhibitors using Grubbs olefin metathesis

The unusual amino acid bishomoallylglycine was synthesized and used to form cyclic P3---P1 tripeptide inhibitors via a Grubbs olefin metathesis method. These compounds show micro- to nanomolar inhibition of Rhizopus chinensis pepsin and represent a new class of simplified aspartic protease inhibitors lacking P′ residues.