Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1975 Dec;151(3):729–739. doi: 10.1042/bj1510729

Synthesis of tritium-labelled isopenicillin N, penicillin N and 6-aminopenicillanic acid.

J J Usher, B Loder, E P Abraham
PMCID: PMC1172422  PMID: 175787

Abstract

1. Phenoxymethylpenicillin sulphoxide 4-methoxybenzyl ester was labelled with 3H in its 2-beta-methyl group. Its specific radioactivity was 362 mCi/mmol. 2. Removal of the side chain of this compound yielded the corresponding ester of 6-aminopenicillanic acid sulphoxide and coupling of the latter with the appropriate protected alpha-aminoadipic acid gave 4-methoxybenzyloxycarbonylisopenicillin N sulphoxide di-4-methoxybenzyl ester or the corresponding derivative of penicillin N. 3. Removal of the protective groups by hydrogenolysis and reduction of the sulphoxide group yielded 3H-labelled isopenicillin N or penicillin N. 4. 3H-labelled phenoxymethylpenicillin sulphoxide was obtained by hydrogenolysis from its 4-methoxybenzyl ester. Reduction of its sulphoxide group and subsequent removal of the side chain gave 3H-labelled 6-aminopenicillanic acid.

Full text

PDF
729

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ABRAHAM E. P., NEWTON G. G. Synthesis of D-delta-amino-delta-carboxyvalerylglycine (a degradation product of cephalosporin N) and of DL-delta-amino-delta-carboxyvaleramide. Biochem J. 1954 Oct;58(2):266–268. doi: 10.1042/bj0580266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. ABRAHAM E. P., NEWTON G. G. The structure of cephalesporin C. Biochem J. 1961 May;79:377–393. doi: 10.1042/bj0790377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BREITENBACH J. W., DERKOSCH J., WESSELY F. Energetics of peptide formation. Nature. 1952 May 31;169(4309):922–922. doi: 10.1038/169922a0. [DOI] [PubMed] [Google Scholar]
  4. COLE M., BATCHELOR F. R. Aminoadipylpenicillin in penicillin fermentations. Nature. 1963;198:383–384. doi: 10.1038/198383a0. [DOI] [PubMed] [Google Scholar]
  5. Chauvette R. R., Pennington P. A., Ryan C. W., Cooper R. D., José F. L., Wright I. G., Van Heyningen E. M., Huffman G. W. Chemistry of cephalosporin antibiotics. XXI. Conversion of penicillins to cephalexin. J Org Chem. 1971 May 7;36(9):1259–1267. doi: 10.1021/jo00808a021. [DOI] [PubMed] [Google Scholar]
  6. Cooper R. D. Structural studies on penicillin derivatives. V. Penicillin sulfoxide-sulfenic acid equilibrium. J Am Chem Soc. 1970 Aug 12;92(16):5010–5012. doi: 10.1021/ja00719a056. [DOI] [PubMed] [Google Scholar]
  7. HALE C. W., NEWTON G. G., ABRAHAM E. P. Derivatives of cephalosporin C formed with certain heterocyclic tertiary bases. The cephalosporin C-A family. Biochem J. 1961 May;79:403–408. doi: 10.1042/bj0790403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. HEILMANN J., BARROLLIER J., WATZKE E. Beitrag zur Aminosäurebestimmung auf Papierchromatogrammen. Hoppe Seylers Z Physiol Chem. 1957;309(4-6):219–220. [PubMed] [Google Scholar]
  9. KATZ A. M., DREYER W. J., ANFINSEN C. B. Peptide separation by two-dimensional chromatography and electrophoresis. J Biol Chem. 1959 Nov;234:2897–2900. [PubMed] [Google Scholar]
  10. Kaiser G. V., Cooper R. D., Koehler R. E., Murphy C. F., Webber J. A., Wright I. G., Van Heyningen E. M. Chemistry of cephalosporin antibiotics. XIX. Transformation of delta2-cephem to delta3-cephem by oxidation-reduction at sulfur. J Org Chem. 1970 Jul;35(7):2430–2433. doi: 10.1021/jo00832a081. [DOI] [PubMed] [Google Scholar]
  11. König W., Geiger R. Eine neue Methode zur Synthese von Peptiden: Aktivierung der Carboxylgruppe mit Dicyclohexycarbodiimid unter Zusatz von 1-Hydroxy-benzotriazolen. Chem Ber. 1970;103(3):788–798. doi: 10.1002/cber.19701030319. [DOI] [PubMed] [Google Scholar]
  12. Manning J. M., Moore S. Determination of D- and L-amino acids by ion exchange chromatography as L-D and L-L dipeptides. J Biol Chem. 1968 Nov 10;243(21):5591–5597. [PubMed] [Google Scholar]
  13. Morin R. B., Jackson B. G., Mueller R. A., Lavagnino E. R., Scanlon W. B., Andrews S. L. Chemistry of cephalosporin antibiotics. XV. Transformations of penicillin sulfoxide. A synthesis of cephalosporin compounds. J Am Chem Soc. 1969 Mar 12;91(6):1401–1407. doi: 10.1021/ja01034a023. [DOI] [PubMed] [Google Scholar]
  14. Smith B., Warren S. C., Newton G. G., Abraham E. P. Biosynthesis of penicillin N and cephalosporin C. Antibiotic production and other features of the metabolism of Cephalosporium sp. Biochem J. 1967 Jun;103(3):877–890. doi: 10.1042/bj1030877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. THOMAS R. Colorimetric detection of penicillins and cephalosporins on paper. Nature. 1961 Sep 16;191:1161–1163. doi: 10.1038/1911161a0. [DOI] [PubMed] [Google Scholar]
  16. Vanderhaeghe H., Vlietinck A., Claesen M., Parmentier G. Preparation of penicillin N and isopenicillin N. J Antibiot (Tokyo) 1974 Mar;27(3):169–177. doi: 10.7164/antibiotics.27.169. [DOI] [PubMed] [Google Scholar]
  17. Wood T. G., Hartline R. A. A synthesis of DL- -aminoadipic acid and its N-chloroacetyl derivative. Anal Biochem. 1971 Sep;43(1):282–287. doi: 10.1016/0003-2697(71)90135-7. [DOI] [PubMed] [Google Scholar]
  18. Wright I. G., Ashbrook C. W., Goodson T., Kaiser G. V., Van Heyningen E. M. Chemistry of cephalosporin antibiotics. 23. 2-Methyl- and 2-methylenecephalosporins. J Med Chem. 1971 May;14(5):420–426. doi: 10.1021/jm00287a011. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES