Penicillamine, a Characteristic Degradation Product of Penicillin

Abstract

WE noticed more than nine months ago that acid hydrolysates of penicillin gave a strong blue-violet coloration with the ninhydrin reagent. Afterwards it was found that, under standardized conditions of hydrolysis, the colour intensity given by numerous penicillin preparations of varying degrees of purity ran parallel to their antibacterial activities except in the case of very crude specimens. It was also found that about 59 per cent of the total nitrogen of the purest preparations could be estimated as amino-nitrogen after one hour's hydrolysis by means of N/10 sulphuric acid under the conditions of the van Slyke method. These facts indicated that the substance responsible for the ninhydrin reaction and the positive results in the van Slyke amino-nitrogen determinations was a fundamental part of the penicillin molecule. Its isolation was therefore regarded as a matter of importance and we are now able to report that it has been obtained as a crystalline hydrochloride. The properties of this substance, which we propose to term penicillamine, show that it represents a novel type of naturally occurring base. Penicillamine is identical with the base which we have stated in an earlier communication1 to occur in acid penicillin hydrolysates.