- Nitrocefin synthesis method
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The invention relates to a nitrocefin synthesis method and belongs to the field of drug synthesis. The invention provides a novel process for preparing nitrocefin from a compound I as a raw material. The compound I is prepared from 7-ACA. The nitrocefin synthesis method can realize synthesis of nitrocefin from 7-ACA as an initial raw material through seven processes. The 7-ACA as an initial raw material is a key intermediate of a cephalosporin, has already been industrialized and has a low market price. The nitrocefin synthesis method has the advantages of simple processes, easy reaction treatment, easy product purification, high yield, easy industrialization and low production cost.
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- A practical synthesis of nitrocefin
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(Chemical Equation Presented). Nitrocefin is a key reagent for high and low throughput assays of the activities of penicillin-binding proteins (PBPs) and β-lactamases, the former used for discovery of antibiotics and the latter for inhibitors of resistance determinants for β-lactam antibiotics. This compound is commercially available but is prohibitively expensive because of the circuitous routes to its synthesis. We describe herein a three-step synthesis of nitrocefin that gives an overall yield of 44%. This is a practical route to the synthesis of this key reagent for drug discovery.
- Lee, Mijoon,Hesek, Dusan,Mobashery, Shahriar
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p. 367 - 369
(2007/10/03)
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- Synthesis of the β-lactamase indicators Cefesone and Nitrocefin
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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.
- Barendse, Nico C. M. E.,Van Der Klein, Pieter A. M.,Verweij, Jan,Witkamp, Henk A.,Van Zoest, Wim J.,De Vroom, Erik
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p. 145 - 147
(2007/10/03)
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