Synthesis and Pharmacological Properties of Deaminotocinamide and a New Synthesis of Tocinamide

Deaminotocinamide (the 20-membered disulfide pentapeptide amide ring of deamino-oxytocin) and tocinamide (the corresponding disulfide pentapeptide amide ring of oxytocin) were synthesized by the stepwise p-nitrophenyl ester method using the p-nitrobenzyl ester for C-terminal carboxyl protection. p-Nitrobenzyl S-benzyl-β-mercaptopropionyltyrosylisoleucylglutaminylasparaginyl-S-benzylcysteinate and p-nitrobenzyl N-benzyloxy-carbonyl-S-benzylcystemyltyrosylisoleucylglutaminylasparaginyl-S-benzylcysteinate were converted to the corresponding C-terminal amide compounds in liquid ammonia. The polypeptide amides were then converted to the corresponding ring compounds by treatment with sodium in liquid ammonia followed by oxidation and purification. Deaminotocinamide was found to possess 34.2 ± 3.0 units/mg of oxytocic activity, but no detectable avian vasodepressor activity. Tocinamide possessed 3.2 ± 0.2 units/mg of oxytocic activity, but no detectable avian vasodepressor activity.