APPLICATION OF RING-CLOSING METATHESIS TO THE SYNTHESIS OF RIGIDIFIEDAMINO-ACIDS AND PEPTIDES

Ruthenium complexes 1a and 1b have been applied to the ring-closing me tathesis (RCM) reactions of a number of dienic substrates. The substra te 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-c ontaining species found in nature. The method was found to function on dienic peptides which were either dissolved in organic solvents or bo und to solid supports.