The Detection of a Schiff Base Intermediate in the Formation of Acetone-oxytocin

Treatment of oxytocin with 60% aqueous acetone at 0° and at a pH of approximately 5 leads to the rapid formation of a Schiff base of oxytocin which has been trapped by reduction with sodium borohydride to give [1-(N-isopropylhemi-L-cystine)]-oxytocin (N-isopropyl-oxytocin). The reduction of the Schiff base was accomplished without reduction of the disulfide bond of oxytocin. Treatment of the hormone with acetone under the same conditions for 24 hr without the addition of borohydride affords acetone-oxytocin in aproximately 50% yield. N-Isopropyl-oxytocin possesses only a trace (~0.1 unit/mg) of oxytocic activity and does not exhibit avian vasodepressor activity. The preparation of N,Nʹ-diisopropyl-L-cystine is also described.