Biosynthesis of penicillins; new crystalline biosynthetic penicillins.

Paper III (1) in this series describes several tests which were found to be useful in determining whether a given compound is utilized by the mold in penicillin formation. To provide proof of the incorporation of various acyl groups into the penicillin molecule and to be able to determine the chemical characteristics and biological properties of the various penicillins, isolation and crystallization were required. Table V in chapter 19 of the penicillin monograph (2) lists some properties of eleven new penicillins. The experimental procedure followed in the preparation of these penicillins is described here. Eighteen additional new penicillins have been crystallized and characterized (cf. Table I). One other penicillin, y-chloroallylmercaptomethylpenicillin has been partially purified but attempts to obtain a crystalline product have been unsuccessful. Each of the penicillins listed except Penicillins 4, 13, 15, 17, and 18 gave satisfactory analytical values. Additional identification was provided in many cases by comparison of the ultraviolet absorption curves of the penicillin and its precursor. It will be noted that p-bromobenzylpenicillin was isolated following the use of N-(r-p-bromophenylbutyryl)-on-valine as precursor. It is apparent that y-substituted butyric acid derivatives are effective in a manner similar to the corresponding substituted acetic acid derivatives and must undergo oxidative degradation with the loss of 2 carbon atoms. Experimental details of the preparation of the precursors used in this work will appear in other papers of this series. Extensive biological tests have been undertaken to compare the properties of natural and biosynthetic penicillins. These studies will be reported elsewhere.