SmI2 reduced thioesters as synthons of unstable acyl radicals: direct synthesis of potential protease inhibitors via intermolecular radical addition.
Aromatic alpha-heterosubstituted thioesters were found to undergo radical 1,4-addition reactions to a series of alpha,beta-unsaturated amides and one ester when subjected to the single electron reducing agent, samarium diiodide, at -78 degrees C. These thioesters derived from alpha-amino acids represent a synthetically useful synthon of unstable acyl radicals. This reaction conveniently provides access to gamma-ketoamides and esters in yields up to 90%, structures that are common in various protease inhibitors derived from peptides. Examples with acryloyl and methacryloyl derivatives of alpha-amino acids and dipeptides lead directly to tri- and tetrapeptide mimetics possessing the gamma-ketoamide functionality. No epimerization was observed with the mild conditions used for these reactions.
Blakskaer
Peter
P
Department of Chemistry, University of Aarhus, Langelandsgade 140, 8000 Aarhus C, Denmark.
Høj
Bettina
B
Riber
Ditte
D
Skrydstrup
Troels
T
D000178:Acrylamides / Q000737:chemistry; D000577:Amides / Q000737:chemistry*; D001593:Benzyl Compounds / Q000737:chemistry; D004952:Esters / Q000737:chemistry; D005609:Free Radicals / Q000737:chemistry; D007454:Iodides / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D010084:Oxidation-Reduction; D011480:Protease Inhibitors / Q000138:chemical synthesis*; D011725:Pyridines / Q000737:chemistry; D012493:Samarium / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D000178:Acrylamides; D000577:Amides; D001593:Benzyl Compounds; D004952:Esters; D005609:Free Radicals; D007454:Iodides; D007659:Ketones; D011480:Protease Inhibitors; D011725:Pyridines; D013438:Sulfhydryl Compounds; D012493:Samarium; C409809:samarium diiodide