title: Discovery of competing anaerobic and aerobic pathways in umpolung amide synthesis allows for site-selective amide 18O-labeling.
abstract: The mechanism of umpolung amide synthesis was probed by interrogating potential sources for the oxygen of the product amide carbonyl that emanates from the α-bromo nitroalkane substrate. Using a series of (18)O-labeled substrates and reagents, evidence is gathered to advance two pathways from the putative tetrahedral intermediate. Under anaerobic conditions, a nitro-nitrite isomerization delivers the amide oxygen from nitro oxygen. The same homolytic nitro-carbon fragmentation can be diverted by capture of the carbon radical intermediate with oxygen gas (O(2)) to deliver the amide oxygen from O(2). This understanding was used to develop a straightforward protocol for the preparation of (18)O-labeled amides in peptides by simply performing the umpolung amide synthesis reaction under an atmosphere of 18O2.
authors.affiliation: Department of Chemistry and Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37235-1822, USA.
authors.forename: Jessica P
authors.initials: JP
authors.lastname: Shackleford
authors.forename: Bo
authors.initials: B
authors.lastname: Shen
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Johnston
mesh_terms: D000332:Aerobiosis; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D000693:Anaerobiosis; D007553:Isotope Labeling / Q000379:methods*; D008956:Models, Chemical; D010103:Oxygen Isotopes
chemical_list: D000577:Amides; D010103:Oxygen Isotopes