Fast and versatile microwave-assisted intramolecular heck reaction in peptide macrocyclization using microwave energy

We have revisited the intramolecular Heck reaction and investigated the microwave-assisted macrocyclization on performed peptides using a model series of ring-varying peptides acrloyl-Gly-[Gly](n)-Phe(4-I)NHR;n = 0-4. The method was applied to both solution and solid supported cyclizations. We demonstrate that the intramolecular Heck reaction can be performed in peptides both in solution and solid support using a modified domestic microwave within 1 to 30 minutes in DMF under reflux with moderate yields ranging from 15 to 25% for a scale between 2-45 mg of linear precursors. The approach was applied to the synthesis of a constrained biologically relevant peptidomimetic bearing an Arg-Gly-Asp (RGD) sequence. These results make the inicrowave-assisted Heck reaction an attractive renovated approach for peptidomimetics. (c) 2005 Wiley Periodicals, Inc.