LABELING OF AMINO ACIDS AND PEPTIDES WITH ISOTOPIC OXYGEN AS FOLLOWED BY 17O-N.M.R.

17O was introduced into the respective α‐ and γ‐COOH groups of Boc‐Gly and Boc‐Glu by saponification of the corresponding O‐methyl esters with 1 N NaOH in H217O. Other 17O enriched Boc‐amino acids were prepared by acid catalyzed exchange into the amino acid α‐COOH group followed by t‐butyloxycarbonylation with t‐butyl S‐4, 6‐dimethylpyrimidin‐2‐ylthio carbonate. Final enrichment, by approximately three orders of magnitude over natural abundance, was 60–100% of the possible maximum. The synthesis of [17O]‐Gly‐Ala, [17O]‐Gly‐Leu and [17O]‐Gly‐Glu by DCC/HBT mediated coupling of Boc‐Gly‐[17'O]‐α‐COOH with amino acid‐O‐t‐butyl esters followed by deprotection with HCl/EtOAc proceeded without undue loss of the isotope. Boc‐[17O]‐Pro‐Leu‐Gly‐NH2 was prepared by a similar procedure. [Tyr2–17O]‐, [Pro7–17O]‐ and [Gly4–17O]‐oxytocin were synthesized using solid phase support. 17O‐chemical shifts of synthetic intermediates and of the final products were as expected for each functional group. Linewidth data correlate with the molecular weights of the compounds prepared.