RAPID inactivation of penicillins F, G, K and X in acid solution was demonstrated at an early date1, and was widely assumed to be a general property until 1954, when phenoxymethylpenicillin (penicillin V) was shown to be relatively stable towards mineral acids2. The recent isolation in these Laboratories of 6-aminopenicillanic acid3 permitted the synthesis of many hitherto inaccessible penicillins, including an extended series of acid-stable α-aryloxyalkylpenicillins4 of which one, α-phenoxyethylpenicillin, is now in clinical use. Both penicillin V and its newer homologues are well absorbed from the gastrointestinal tract and hence can be given by mouth, but they show useful antibacterial activity only against Gram-positive bacteria. Benzylpenicillin (penicillin G) has a broader antibacterial spectrum, but is not suitable for oral administration. We therefore prepared a series of α-substituted benzyl penicillins (I) in the hope of finding an acid-stable penicillin active against Gram-negative as well as Gram-positive bacteria.
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Benedict, R. G., Schmidt, W. H., and Coghill, R. D., J. Bact., 51, 291 (1946); cf. Clutterbuck, P. W., Lovell, R., and Raistrick, H., Biochem. J., 26, 1907 (1932).
Brandl, E., and Margreiter, H., Oesterr. Chem. Z., 55, 11 (1954).
Batchelor, F. R., Doyle, F. P., Nayler, J. H. C., and Rolinson, G. N., Nature, 183, 257 (1959). Doyle, F. P., Nayler, J. H. C., and Rolinson, G. N., Brit. Pat. Spec. No. 870,396 (1961).
Perron, Y. G., Minor, W. F., Holdrege, C. T., Gottstein, W. J., Godfrey, J. C., Crast, L. B., Babel, R. B., and Cheney, L. C., J. Amer. Chem. Soc., 82, 3934 (1960).
Doyle, F. P., Nayler, J. H. C., and Smith, H., Brit. Pat. Spec. No.873,049 (1961).
Ford, J. H., Indust. Eng. Chem., Anal. Ed., 19, 1004 (1947).
Johnson, J. R., Woodward, R. B., and Robinson, R., in The Chemistry of Penicillin, 445 (Princeton Univ. Press, 1949). Abraham, E. P., Giornale di Microbiologica, 2, 102 (1956).
Rolinson, G. N., and Stevens, S., Brit. Med. J., ii, 191 (1961).
Brown, D. M., and Acred, P., Brit. Med. J., ii, 197 (1961).
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DOYLE, F., NAYLER, J., SMITH, H. et al. Some Novel Acid-stable Penicillins. Nature 191, 1091–1092 (1961). https://doi.org/10.1038/1911091a0
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