SYNTHESIS AND SOME PHARMACOLOGICAL ACTIVITIES OF [4-L-NORVALINE]-OXYTOCIN AND [4-L-NORLEUCINE]-OXYTOCIN AND THEIR DEAMINO ANALOGS

[4-Norvaline]-oxytocin, [1-deamino,4-norvaline]-oxytocin, [4-norleucine]-oxytocin, and [1-deamino,4-nor-leucine]-oxytocin have been synthesized from the requisite protected polypeptide precursors, which were prepared by the stepwise p-nitrophenyl ester method. The compounds were isolated by countercurrent distribution followed by partition chromatography on Sephadex G-25 and then tested for a number of pharmacological activities. The avian vasodepressor potencies were found to be 99, 128, 51, and 53 units mg, respectively; the oxytocic potencies 61, 56, 20.5, and 12.8 units/mg, respectively; and the milk-ejecting potencies 182, 134, 87, and 50 units/mg, respectively. The antidiuretic and pressor activities of all four analogs were extremely low or negligible. © 1969, American Chemical Society. All rights reserved.