Synthesis of novel cyclic protease inhibitors using Grubbs olefin metathesis

The unusual amino acid bishomoallylglycine was synthesized and used to form cyclic P 3P 1 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. Cyclic P 3-P 1 tripeptide inhibitors were formed via a Grubbs olefin metathesis method. These compounds show micro- to nanomolar inhibition of Rhizopus chinensis pepsin.