Application of ring-closing metathesis to the synthesis of rigidified amino acids and peptides

Ruthenium complexes 1a and 1b have been applied to the ring-closing metathesis (RCM) reactions of a number of dienic substrates. The substrate scope includes rings of 6 to 20 members. In addressing macrocyclic peptides, a class of tetrapeptide disulfides inspired the synthesis of the carbon-carbon bond analogs. Replacement of cysteine residues with allylglycines resulted in the acyclic precursors which were subjected to RCM to afford the corresponding macrocycles. In addition, several macrocycles were prepared which were not based upon disulfide-bridge-containing species found in nature. The method was found to function on dienic peptides which were either dissolved in organic solvents or bound to solid supports.