Direct entry to peptidyl ketones via SmI2-mediated C-C bond formation with readily accessible N-peptidyl oxazolidinones.
In this work, a new method for the preparation of peptidyl ketones is presented employing a SmI(2)/H(2)O-mediated coupling of N-peptidyl oxazolidinones with electron-deficient alkenes. The requisite peptide imides were easily prepared by solution-phase peptide synthesis starting from an N-acyl oxazolidinone derivative of an amino acid. Importantly, they could be used directly in the C-C bond-forming step without the need for further functionalization. Coupling of these peptide derivatives with a second peptide possessing an N-terminal acryloyl group leads to ketomethylene isosteres of glycine-containing peptides. This method represents an alternative means for ligating two small peptides through a C-C bond-forming step.
Mittag
Tina
T
Center for Insoluble Protein Structures, Department of Chemistry and Interdisciplinary Nanoscience Center, University of Aarhus, Langelandsgade 140, 8000 Aarhus C, Denmark.
Christensen
Kasper L
KL
Lindsay
Karl B
KB
Nielsen
Niels Christian
NC
Skrydstrup
Troels
T
D000178:Acrylamides / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D007454:Iodides / Q000737:chemistry*; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D023303:Oxazolidinones / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D012493:Samarium / Q000737:chemistry*
D000178:Acrylamides; D000588:Amines; D000596:Amino Acids; D005609:Free Radicals; D007454:Iodides; D007659:Ketones; D023303:Oxazolidinones; D010455:Peptides; D012493:Samarium; D002244:Carbon; C409809:samarium diiodide; C115287:tert-butylacrylamide