A simple and economical method for the production of 13C,18O-labeled Fmoc-amino acids with high levels of enrichment: applications to isotope-edited IR studies of proteins.

Isotope-edited IR of proteins has generated considerable interest. Double labeling with 13C and 18O with high levels of isotopic enrichment is required for residue-specific resolution. Current methods for the preparation of doubly labeled amino acids give modest 18O enrichment, limiting the utility of the approach. We report a simple and economical method for preparing 13C,18O-doubly labeled N-(9-fluorenylmethoxycarbonyl)amino acids with high levels of enrichment for residues that do not require acid-labile side-chain protecting groups.