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.
Byk
Gerardo
G
Bar Ilan University, Department of Chemistry, Laboratory of Peptidomimetics and Genetic Chemistry, Ramat Gan, Israel. bykger@mail.biu.ac.il
Cohen-Ohana
Mirit
M
Raichman
Daniel
D
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D019281:Dimerization; D004126:Dimethylformamide / Q000737:chemistry; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008872:Microwaves; D008970:Molecular Weight; D009842:Oligopeptides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000528:radiation effects*; D011487:Protein Conformation; D012996:Solutions; D013329:Structure-Activity Relationship
D000596:Amino Acids; D009842:Oligopeptides; D010456:Peptides, Cyclic; D012996:Solutions; C047981:arginyl-glycyl-aspartic acid; D004126:Dimethylformamide