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1-(N-Methyl-hemi-~-cystine)]-oxytocin, an analog of the posterior pituitary hormone oxytocin in which one of the hydrogens of the free amino group is replaced by a methyl group, has been synthesized and tested for biological activity. Preparations of this analog (N-methyl-oxytocin) were found to differ markedly in biological potency and it was suspected that this variation might be due to the presence of varying amounts of oxytocin as a trace contaminant. The N-methyl-S-benzylcysteine used in the synthetic procedures may have contained undetectable traces of S-benzylcysteine which, if present, could account for the eventual formation of trace amounts of oxytocin. For removal of any oxytocin present, an N-methyl-oxytocin preparation was treated with acetone, since it was found that N-methyl-oxytocin reacts with acetone to only a slight extent under conditions (80z aqueous acetone, 22 hr) which convert oxytocin almost quantitatively to "acetone-oxytocin." Small amounts of "acetoneoxytocin" and "acetone-N-methyl-oxytocin" were formed and were readily separated from unreacted N-methyloxytocin by partition chromatography on Sephadex G-25. N-Methyl-oxytocin purified in this manner was found to possess approximately 2 units/mg of oxytocic activity, compared with 500 units/mg for oxytocin. "Acetone-N-methyl-oxytocin" was formed in higher yield by treatment of the N-methyl-oxytocin with 80 % aqueous acetone for 7 days and was isolated and purified by partition chromatography and gel filtration on Sephadex G-25.Abstract: The biosynthesis of vindoline in Vinca rosea plants has been investigated using appropriate radioactive precursors. The results obtained are in full accord with the suggested monoterpenoid origin for the nontryptophan-derived portion of the indole alkaloids.
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