Synthèse de la (N‐méthyl‐Tyr)²‐oxytocine

Different methods have been investigated for the preparation of N‐CBO‐S‐benzyl‐ L ‐cysteinyl‐N‐methyl‐ L ‐tyrosyl‐ L ‐isoleucine. Condensation of this protected tripeptide with L ‐glutaminyl‐ L ‐asparaginyl‐S‐benzyl‐ L ‐cysteinyl‐ L ‐prolyl‐ L ‐leucyl‐glycinamide affords N‐CBO‐ S ‐benzyl‐ L ‐cysteinyl‐N ‐methyl‐ L ‐tyrosyl‐ L ‐isoleucyl‐ L ‐glutaminyl‐ L ‐ asparaginyl‐S‐benzyl‐ L ‐cysteinyl‐ L ‐prolyl‐ L ‐leucyl‐glycinamide. Cleavage of the protecting groups of the resulting nonapeptide with sodium in liquid ammonia, oxidation with air in dilute aqueous solution and purification by counter‐current distribution gives the desired cyclic nonapeptide amide : (N‐methyl‐Tyr) 2 ‐oxytocin. This exhibits less than one per cent of the oxytocic potency of oxytocin.