PENICILLIN 101 



military needs could be met only if laboratory synthesis were accomplished. 

 A practical synthesis of penicillin has, however, not yet been realized, al- 

 though a sj^nthesis has been reported by duVigneaud, et at. (1946). Fortu- 

 nately, the production by fermentation processes proved adequate for all 

 WHY needs. 



So far, six naturally occurring penicillins have been isolated in the pure 

 state and all have the empirical chemical formula C9H11O4SN2R. The sig- 

 nificant penicillin activity is resident in the CyHii04SN2 grouping and all 

 of the penicillins show the same qualitative action against microorganisms. 

 The quantitative differences in potency (from 900-2300 units per mg.) be- 

 tween the penicillins are dependent on the nature of the R group. In peni- 

 cillin F, R is A 2-pentenyl; in Dihydropenicillin F (produced by Aspergillus 

 giganteus), R is N-amyl; in flavicidin (produced by A. flavus), R is A 3- 

 pentenyl; in penicillin G, R is benzyl; in penicillin X, R is p-hydroxybenzyl; 

 and in penicillin K, R is N-heptyl. Of these compounds, penicillin X, first 

 isolated by Stodola, Wachtel, and Coghill of the Northern Laboratory, is 

 of unusual interest in that new, highly active penicillins can be produced 

 from it by substitution reactions (Stodola, et al.^). 



A brief summary of the results obtained by British and American chem- 

 ists was published in Science in 1945 bj^ the Committee on Medical Re- 

 search, O.S.R.D. (Washington) and the Medical Research Council (Lon- 

 don); details, however, will not be available until the appearance of the 

 Monograph entitled "The Chemistry of Penicillin," now in preparation 

 under the auspices of the National Academy of Sciences and the Office of 

 Scientific Research and Development, soon to be published by the Piince- 

 ton University Press. Two short excerpts from this Monograph were 

 pubhshed in Science in 1947 (105: 653-659 and 106: 503-505). 



Penicillinase 



Penicillin is rapidly destroyed by enzymes, termed penicillinases, that 

 are elaborated by a number of common Gram-negative and certain Gram- 

 positive species of bacteria. The production, purification, and character- 

 ization of penicillinases have been studied by Benedict, et al. (1945a), Wood- 

 mff and Foster (1945), Perlstein and Liebmann (1945a and 1945b), 

 McQuarrie, et al. (1944), and LePage, et al. (1946). In the commercial 

 production of penicillin, penicillinase preparations of high purity find an 

 important role in the testing of the drug for sterility. Parallel with 

 investigations on the enzymatic destruction of penicillin, Benedict, et al. 

 (1945, 1946b) studied the breakdown of the drug at various temperatures 

 and pH levels. 



1 To be published in the forthcoming Monograph entitled, "The Chemistry of 

 Penicillin." 



