Play all audios:
![ABSTRACT FOLLOWING on the isolation in these Laboratories of 6-aminopenicillanic acid1, we have used it to synthesize many novel penicillins, with particular emphasis on structures which resist inactivation by staphylococcal penicillinase. One class of penicillins possessing this valuable property has been obtained by acylating 6-aminopenicillanic acid with aromatic or heteroaromatic carboxylic acid chlorides substituted in both _ortho_ positions. When the ring structure of the side-chain acid is six-membered, almost any pair of _ortho_ substituents confer marked stability towards penicillinase, but when it is five-membered one or both of the substituents must be relatively bulky, for example, phenyl or substituted phenyl. Such findings illustrate the primary importance of steric effects in determining stability towards penicillinase. In this respect the chemical constitution of the side-chain is of much less significance, although it has a profound influence on antibacterial activity and on stability towards acids. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 51 print issues and online access $199.00 per year only $3.90 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS DESIGN AND SYNTHESIS OF 4-[4-FORMYL-3-(2-NAPHTHYL)PYRAZOL-1-YL]BENZOIC ACID DERIVATIVES AS POTENT GROWTH INHIBITORS OF DRUG-RESISTANT _STAPHYLOCOCCUS AUREUS_ Article 29 June 2020 WYCHIMICINS, A NEW CLASS OF SPIROTETRONATE POLYKETIDES FROM _ACTINOCRISPUM WYCHMICINI_ MI503-A4 Article 07 September 2022 STRUCTURAL ANALYSIS SHOWS THE MODE OF INHIBITION FOR _STAPHYLOCOCCUS AUREUS_ LIPASE BY ANTIPSYCHOTIC PENFLURIDOL Article Open access 14 April 2025 REFERENCES * 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. 870, 396 (1961). Article ADS CAS Google Scholar * Doyle, F. P., Hardy, K., Nayler, J. H. C., Soulal, M. J., Stove, E. R., and Waddington, H. R. J., _J. Chem. Soc._ (in the press). * Doyle, F. P., and Nayler, J. H. C., U.S. Patent Spec. 2, 996, 501 (1961). * Doyle, F. P., Nayler, J. H. C., Smith, H., and Stove, E. R., _Nature_, 191, 1091 (1961). Article ADS CAS Google Scholar Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Organic Chemistry Department, Beecham Research Laboratories, Ltd., Brockham Park, Betchworth, Surrey F. P. DOYLE, A. A. W. LONG, J. H. C. NAYLER & E. R. STOVE Authors * F. P. DOYLE View author publications You can also search for this author inPubMed Google Scholar * A. A. W. LONG View author publications You can also search for this author inPubMed Google Scholar * J. H. C. NAYLER View author publications You can also search for this author inPubMed Google Scholar * E. R. STOVE View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE DOYLE, F., LONG, A., NAYLER, J. _et al._ New Penicillins Stable towards Both Acid and Penicillinase. _Nature_ 192, 1183–1184 (1961). https://doi.org/10.1038/1921183a0 Download citation * Issue Date: 23 December 1961 * DOI: https://doi.org/10.1038/1921183a0 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative](https://media.springernature.com/w215h120/springer-static/image/art%3A10.1038%2Fs41429-020-0341-2/MediaObjects/41429_2020_341_Fig1_HTML.png)
ABSTRACT FOLLOWING on the isolation in these Laboratories of 6-aminopenicillanic acid1, we have used it to synthesize many novel penicillins, with particular emphasis on structures which
resist inactivation by staphylococcal penicillinase. One class of penicillins possessing this valuable property has been obtained by acylating 6-aminopenicillanic acid with aromatic or
heteroaromatic carboxylic acid chlorides substituted in both _ortho_ positions. When the ring structure of the side-chain acid is six-membered, almost any pair of _ortho_ substituents confer
marked stability towards penicillinase, but when it is five-membered one or both of the substituents must be relatively bulky, for example, phenyl or substituted phenyl. Such findings
illustrate the primary importance of steric effects in determining stability towards penicillinase. In this respect the chemical constitution of the side-chain is of much less significance,
although it has a profound influence on antibacterial activity and on stability towards acids. Access through your institution Buy or subscribe This is a preview of subscription content,
access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 51 print issues and online access $199.00 per year only $3.90 per issue Learn
more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS
OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS DESIGN AND SYNTHESIS OF
4-[4-FORMYL-3-(2-NAPHTHYL)PYRAZOL-1-YL]BENZOIC ACID DERIVATIVES AS POTENT GROWTH INHIBITORS OF DRUG-RESISTANT _STAPHYLOCOCCUS AUREUS_ Article 29 June 2020 WYCHIMICINS, A NEW CLASS OF
SPIROTETRONATE POLYKETIDES FROM _ACTINOCRISPUM WYCHMICINI_ MI503-A4 Article 07 September 2022 STRUCTURAL ANALYSIS SHOWS THE MODE OF INHIBITION FOR _STAPHYLOCOCCUS AUREUS_ LIPASE BY
ANTIPSYCHOTIC PENFLURIDOL Article Open access 14 April 2025 REFERENCES * 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. 870, 396 (1961). Article ADS CAS Google Scholar * Doyle, F. P., Hardy, K., Nayler, J. H. C., Soulal, M. J., Stove, E. R., and
Waddington, H. R. J., _J. Chem. Soc._ (in the press). * Doyle, F. P., and Nayler, J. H. C., U.S. Patent Spec. 2, 996, 501 (1961). * Doyle, F. P., Nayler, J. H. C., Smith, H., and Stove, E.
R., _Nature_, 191, 1091 (1961). Article ADS CAS Google Scholar Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Organic Chemistry Department, Beecham Research
Laboratories, Ltd., Brockham Park, Betchworth, Surrey F. P. DOYLE, A. A. W. LONG, J. H. C. NAYLER & E. R. STOVE Authors * F. P. DOYLE View author publications You can also search for
this author inPubMed Google Scholar * A. A. W. LONG View author publications You can also search for this author inPubMed Google Scholar * J. H. C. NAYLER View author publications You can
also search for this author inPubMed Google Scholar * E. R. STOVE View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and
permissions ABOUT THIS ARTICLE CITE THIS ARTICLE DOYLE, F., LONG, A., NAYLER, J. _et al._ New Penicillins Stable towards Both Acid and Penicillinase. _Nature_ 192, 1183–1184 (1961).
https://doi.org/10.1038/1921183a0 Download citation * Issue Date: 23 December 1961 * DOI: https://doi.org/10.1038/1921183a0 SHARE THIS ARTICLE Anyone you share the following link with will
be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt
content-sharing initiative