Multiple-turnover isotopic labeling of Fmoc- and Boc-protected amino acids with oxygen isotopes.

An efficient method for the selective isotopic labeling of carboxylic acids is reported. By reacting an amino acid with excess carbodiimide and (18)OH(2), a kinetically enhanced multiple turnover reaction provides the (18)O-labeled product in high yield and excellent isotopic enrichment. This reaction is fully compatible with standard Fmoc, Boc, Trt, and OtBu protecting groups and provides a means to selectively label the alpha-carboxylic acids of functionalized amino acids with stable oxygen isotopes.