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Synthesis 1998; 1998(2): 145-147
DOI: 10.1055/s-1998-2018
short paper
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Synthesis of the β-Lactamase Indicators Cefesone and Nitrocefin

Nico C. M. E. Barendse* , Pieter A. M. van der Klein, Jan Verweij, Henk A. Witkamp, Wim J. van Zoest, Erik de Vroom
  • *Gist-brocades B.V., P.O. Box 1, NL-2600 MA Delft, The Netherlands; E-mail: ERIK.DE VROOM@GIST-BROCADES.INFONET.COM
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Publication Date:
31 December 2000 (online)

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The synthesis of the β-lactamase indicators Cefesone [(6R,7R)-3-(2,4-dinitrostyryl)-7-(phenylacetamido)ceph-3-em-4-carboxylic acid] and Nitrocefin [(6R,7R)-3-(2,4-dinitrostyryl)-7-(2-thienylacetamido)ceph-3-em-4-carboxylic acid] from tert-butyl (1S,6R,7R)-3-bromomethyl-1-oxo-7-(phenylacetamido)ceph-3-em-4-carboxylate is reported. Phosphonylation of the latter compound with triphenylphosphine gave the corresponding phosphonium derivative in 93% yield. Reduction followed by Wittig coupling with 2,4-dinitrobenzaldehyde gave a 1 : 12 mixture of E- and Z-isomers in 83% yield. The tert-butyl protecting group was removed with titanium tetrachloride to give Cefesone as the pure crystalline E-isomer in 63% yield. De-acylation was achieved by enzymatic hydrolysis in 77% yield. Finally the 2-thienylacetyl side chain was introduced to give crystalline Nitrocefin in 67% yield.

Cefesone - cephalosporin - Nitrocefin - β-lactamase indicator - penicillin acylase

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