Ammonia Oxytocin

K Kuromizu, J Meienhofer. Removal of the JW-benzyloxycarbonyl group from cysteine-containing peptides by catalytic hydrogenolysis in liquid ammonia, exemplified by a synthesis of oxytocin. J Am Chem Soc 96, 4978, 1974. 

In the event, the chemists needed a group that they could later react with ammonia to make the primary amide that is present in oxytocin. They also wanted a group that was stable to mild acid—so they chose the ethyl ester. 

At this point it is interesting to note, that the method of reducing disulfides with sodium in liquid ammonia [16], benzylation of the thiol groups in situ and their debenzylation in the same solvent [17] had been elaborated by du Vigneaud many years earher (cf, p. 71) as if some intuition would have directed his efforts toward the chemistry of oxytocin. An account of this continued interest in sulfur containing natural products can be found in his book A Trail of Research [18]. 

PRACTICE PROBLEM 24.10 Treating oxytocin with certain reducing agents (e.g., sodium in liquid ammonia) brings... 

The synthesis of oxytocin using the S-ethylmercapto group [13] indicated that the AT-t-amyloxycarbonyl group could be removed with trifluoroacetic acid without apparent acid-catalyzed disulphide interchange of the S-ethylmercapto group. Surprisingly the unsymmetrical disulphide was also stable to the action of 25% ammonia in methanol during the ammonolysis of (70). 

Sodium in liquid ammonia brings about reductive cleavage of the disulfide linkage of oxytocin to two thiol groups then air oxidizes the two thiol groups back to a disulfide... 

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