Design and Synthesis of Potential Macrocyclic Zinc Metalloprotease Inhibitors

Abstract

A series of succinate-derived macrocyclic amides 1 were synthezized using ring-closing metathesis in the key step. The substrate scope includes rings of 11 to 14 members. The cyclic dicarboxylic acids 1 represent a family of new model compounds for potential zinc metalloprotease inhibitors. The metathesis precursors were provided by amide coupling of tert-butyl 3-carboxyhex-5-enoate 2 with numerous side chain alkenylated amino acid esters of general type 3 derived from L-tyrosine and L-cysteine.