Synthesis and some pharmacological properties of oxytocin analogues having L-thiazolidine-4-carboxylic acid in position 7

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Abstract
[7-(Thiazolidine-4-carboxylic acid)]oxytocin and [1-.beta.-mercaptopropionic acid,7-(thiazolidine-4-carboxylic acid)]oxytocin were synthesized by a solid-phase method. .alpha.-N-tert-Butoxycarbonyl- and S-ethylcarbamoyl-protecting groups were employed. The dipeptide Boc-Cys(Ec)-thiazolidine-4-carboxylic acid and individual residues was coupled to a H-Gly-dehydroalanine-resin with dicyclohexylcarbodiimide in the presence of 1-hydroxybenzotriazole. The appropriate protected polypeptide intermediates were cleaved from the resin by acidolysis, deprotected in NH3, and oxidized to the cyclic disulfide analogues with ICH2CH2I [diiodoethylene]. Purification was effected by partition chromatography and gel filtration. Relative to oxytocin and [1-.beta.-mercaptopropionic acid]oxytocin, these analogues exhibit greatly enhanced oxytocic and avian vasodepressor potencies and unchanged rat pressor protencies.