Side chain stereoisomerism and antista-phylococcal potency of penicillins.


Penicillins may be regarded as acylation products of 6-aminopenicillanic acid (Figure 1). This bicyclic dipeptide results from cyclization of L-Cysteinyl-L-valine (1) and is loosed into the culture medium in good yield when a strain of Penicillium chrysogenurn (W.51.20) is cultured in the absence of side chain precursors suitable for acylation at the 6-amino grouping (2). With the attainment of commercially feasible fermentive production of 6-aminopenicillanic acid, the organic chemist can now carry out industrially practical terminal synthesis of known or new penicillins. Alpha-phenoxyethylpenicillin [penicillin B, 6(a-phenoxypropioamido)-penicillanate, or phenethicillin-see Figure 1], the first marketed product of such industrial terminal penicillin synthesis, has not been identified as a naturally occurring penicillin. Special biological properties have been ascribed to this compound which also distinguish it from other penicillins (3-5). These include: 1) resistance to acid (gastric) degradation; 2) excellent absorption from the gastrointestinal tract; 3) greater antibacterial potency. Slow penicillinase inactivation quite reasonably would be reflected in apparent in vitro superiority in antibacterial effectiveness against penicillinaseproducing bacteria. However, enhanced antibacterial effectiveness against nonpenicillinase-elaborating bacteria would require other explanation. In part, the augmented antibacterial potency claimed for a-phenoxyethylpenicillin has been ascribed to the stereoisomerism inherent in the a-phenoxyethyl side chain characteristic of this penicillin. The L-isomer was reported to be generally more active than the D-isomer, and the racemate 1 more effective than either enantimorph

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@article{Hoeprich1961SideCS, title={Side chain stereoisomerism and antista-phylococcal potency of penicillins.}, author={Paul D. Hoeprich}, journal={The Journal of clinical investigation}, year={1961}, volume={40}, pages={783-93} }