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 preformed peptides using a model series of ring‐varying peptides acryloyl‐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 microwave‐assisted Heck reaction an attractive renovated approach for peptidomimetics. © 2005 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 84: 274–282, 2006 This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com