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Published on: January 26, 2016
Fast and versatile microwave-assisted intramolecular Heck reaction in peptide macrocyclization using microwave energy
Gerardo Byk1, Mirit Cohen-Ohana, Daniel Raichman
1Bar Ilan University, Department of Chemistry, Laboratory of Peptidomimetics and Genetic Chemistry, Ramat Gan, Israel. bykger@mail.biu.ac.il
Abstract:
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.
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