Process for the low-racemization preparation of peptide intermediates of the synthesis of gonadorelin and gonadorelin analogs, and new intermediates for this process

US4691008A · kind A · utility

Assignee

• Hoechst GmbH · DE

Inventors

• Rainer Uhmann · Kriftel, DE
• Kurt Radscheit · Kelkheim, DE

Key dates

• Filing date: Mar 25, 1985
• Grant date: Sep 1, 1987
• Expiry date: Mar 25, 2005

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y10S930/13
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The invention relates to a process for the preparation of peptides of the formula I EQU U--A.sup.1 --A.sup.2 13 A.sup.3 --A.sup.4 --A.sup.5 --X (I) in which PA0 U denotes a urethane protective group, PA0 A.sup.1 denotes Trp or D-Trp, PA0 A.sup.2 denotes Ser, Ala or Thr, PA0 A.sup.3 denotes Tyr or Phe, PA0 A.sup.4 denotes Gly, the residue of a D-amino acid or the residue of a D-amino acid derivative, PA0 A.sup.5 denotes Leu, N-methyl-Leu, N-ethyl-Leu, Ser(Bu.sup.t), Cys(But), Asp(OBu.sup.t), Glu(OBu.sup.t), Orn(Boc) or Lys(Boc) and PA0 X denotes OBu.sup.t or A.sup.6 --Pro--Y, where PA0 A.sup.6 represents Arg, Orn, Lys or homoarginine, and PA0 Y represents Gly--NH.sub.2, NH--NH--CO--NH.sub.2, (C.sub.1 -C.sub.3)-alkylamino, cyclopropylamino, (C.sub.1 -C.sub.3)-alkylamino which is substituted with hydroxyl or fluorine, or cycloalkylamino which is substituted with hydroxyl or fluorine, using tripeptides of the formula II, EQU U--A.sup.1 --A.sup.2 --A.sup.3 --OH, in which the residues are defined as above. The invention also relates to peptides of the formula II as intermediates in this process.