Collect. Czech. Chem. Commun. 1984, 49, 642-652

Synthesis and properties of oxytocin analogues modified in the tripeptide side chain

Zdenko Procházka, Michal Lebl, Tomislav Barth, Jan Hlaváček, Antonín Trka, Miloš Buděšínský and Karel Jošt

Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, 166 10 Prague 6


Two oxytocin analogues were synthesized by fragment condensation (6 + 3) in the presence of dicyclohexylcarbodiimide and 1-hydroxybenzotriazole. In one of the analogues, proline in the position 7 and leucine in the position 8 were substituted by 2-[1-(2-oxo-3-aminopyrrolidinyl)]-4-methylpentanoic acid, in the other proline was replaced by 1-aminocyclopropane-1-carboxylic acid. Biological activities of the first analogue were strongly reduced and dissociation of the uterotonic and galoctogogic activities was observed with both the analogues. The structure of 2-(3-tert-butyloxycarbonylaminopyrrolidin-2-on-1-yl)-4-methylpentanoylglycine and its amide was confirmed by mass and 1 H NMR spectroscopy.