Synthesis of [3’, 5’-¹³C₂]Tyrosine and Its Use in the Synthesis of Specifically Labeled Tyrosine Analogues of Oxytocin and Arginine-Vasopressin and Their 2-D-Tyrosine Diastereoisomers

DL-[3', 5'-¹³C₂]Tyrosine (91% ¹³C enriched) was synthesized by a ten-step synthetic scheme in an overall yield of 22% (86+% per step) using [l, 3-¹³C₂]acetone as the source of label. The enantiomers were resolved by enzymatic methods, and the labeled DL amino acid or purified enantiomers readily converted to the N^α-Boc acids suitable for peptide synthesis. BOC-DL-[3', 5'-¹³C₂]tyrosine was used for the total synthesis of the specifically labeled peptide hormone derivatives [2-DL-[3',5'-¹³C₂]tyrosine]oxytocin and [2-DL-[3',5,-¹³C₂]tyrosine, 8-arginine]vasopressin by solid phase methods. The diastereoisomers were separated from each other by partition chromatography on Sephadex G-25 followed by gel filtration to give the following specifically labeled hormone derivatives : [2-[3',5'-^l3C₂]tyrosine]oxytocin, [2-D-[3',5'-¹³C₂]tyrosine]oxytocin, [2-[3',5'-¹³C₂]tyrosine, 8-arginine]vasopressin, and [2-D-[3', 5'-¹³C₂]tyrosine, 8-arginine]vasopressin. The milk ejecting activities were determined.