Synthesis of Specific Deuterium Labeled Tyrosine and Phenylalanine Derivatives and Their Use in the Total Synthesis of [8-Arginine]vasopressin Derivatives: The Separation of Diastereomeric [8-Arginine]vasopressin Derivatives by Partition Chromatography1,2

Diane M. Yamamoto, Donald A. Upson, David K. Linn, Victor J. Hruby

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Derivatives of tyrosine specifically deuterated at the α carbon ([α-2H1] tyrosine) and at both the a and Β carbons ([α,Β,Β-2H3]tyrosine) and a derivative of phenylalanine specifically deuterated at the α carbon ([α-2H1]phenylalanine) have been synthesized in high yield. These labeled compounds have been resolved enzymatically, and the enantiomers and racemates have been converted to N-tert-butyloxycarbonyl derivatives. The deuterium labels were not exchanged under the conditions of the syntheses. The protected derivatives as well as specifically deuterated derivatives of S-benzylcysteine and of glycine were used to prepare specifically deuterated analogues of [8-arginine]vasopressin using solid phase peptide procedures. The use of improved synthetic procedures resulted in considerable improvements in the yields of [8-arginine]vasopressin compared with previous reports. In addition, new solvent systems for partition chromatography purification of [8-arginine]vasopressin on Sephadex were developed which allowed a facile one-step separation of diastereomers of [8-arginine]vasopressin containing a racemic amino acid at either the l-hemicystine or the 2-tyrosine positions of the hormone. The following specifically deuterated hormone derivatives were synthesized: [9-[α,α-2H2]glycinamide,8-arginine]vasopressin (15), [l-hemi-[α-2H1]cystine,8-arginine]vasopressin (21), [l-hemi[Β,(Β-2H2]cystine,8-arginine]vasopressin (17), [2-[α-2H1]tyrosine,8-arginine]vasopressin (19a), [2-[α,Β,Β-2H3]tyrosine,8-arginine]vasopressin (20), [3-[α-2H1]phenylalanine,8-arginine]vasopressin (18a), [1-hemi-D-[α-2H1]cystine,8-arginine]vasopressin (16), [2-D-[α,-2H1]tyrosine,8-arginine]vasopressin (19b), [l-hemi-D-cystine,3-[α-2H1]phenylalanine,8-arginine]vasopressin (18b).

Original languageEnglish (US)
Pages (from-to)1564-1570
Number of pages7
JournalJournal of the American Chemical Society
Volume99
Issue number5
DOIs
StatePublished - Jan 1 1977

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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