Process for preparing the releasing hormone of luteinizing hormone (LH) and of follicle stimulating hormone (FSH), salts and compositions thereof, and intermediates therefor

US4159980A · kind A · utility

Assignee

• Amerimas Home Products, Inc. · US

Inventors

• Hans U. Immer · Mount Royal, CA
• Verner R. Nelson · Montréal, CA
• Manfred Götz · Brakel, DE

Key dates

• Filing date: Mar 29, 1974
• Grant date: Jul 3, 1979
• Expiry date: Mar 29, 1994

Classification

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

Abstract

A process for preparing the LH- and FSH-releasing hormone of the formula I EQU h-- pyr-- His-- Trp-- Ser-- Tyr-- Gly-- Leu-- Arg-- Pro-- Gly-- NH.sub.2 which comprises the following steps: Condensing N-(5-oxo-L-prolyl)-L-histidine hydrazide by means of the azide method with L-tryptophan benzyl ester and treating the resulting compound with hydrazine hydrate to obtain N-[N-(5-oxo-L-prolyl)-L-histidyl]-L-tryptophan hydrazide (II); treating N-[O-benzyl-N-carboxy-L-tyrosyl]glycine N-benzyl ester with ethyl chloroformate to obtain the corresponding mixed anhydride which is reacted with t-butyl carbazate to obtain the corresponding 2-carboxyhydrazide t-butyl ester which is hydrogenolyzed to N-L-tyrosylglycine 2-carboxyhydrazide t-butyl ester, and condensing the latter with N-carboxy-L-seryl N-benzyl ester 2,4-dinitrophenyl ester followed by hydrogenolysis of the reaction product to obtain N-(N-L-seryl-L-tyrosyl)glycine 2-carboxyhydrazide t-butyl ester (III); condensing N-carboxy-L-proline N-benzyl ester with glycine ethyl ester in the presence of dicyclohexylcarbodiimide, treating the resulting product with ammonia and then hydrogenolyzing, to obtain 2-[(L-prolyl)amino]acetamide, which i…