Chemistry of Cephalosporin Antibiotics. X.1 Synthesis of Methyl 3-Formyl-7-(thiophene-2-acetamido)-3-cephem-4-carboxylate, a New Cephalosporin Derivative
“…After reviewing this literature, and determining the fermentation/extraction and chemical processing changes which would be required to commercialize a process scheme based on intermediate 6 or 8 we were dissuaded from pursuing such a route. In brief, as is the case in utilizing 4 and 5 , evaluation of the published chemical methods for converting 3-substituted cephalosporins to the desired 3-H cephalosporins from a cost standpoint revealed that we would need to undertake a great deal of exploratory work to even be in a position to determine which of the many raw chemical recipes from this research literature 10 might be improved, integrated, and developed to create an economically attractive process. In addition our evaluation indicated that a relatively large investment in new process equipment would be needed.…”
Analysis of several options for the synthesis of Ceftibuten from
cephalosporin C-derived starting materials led to the conclusion
that the most practical option, leading to the lowest costs, would
be realized by trying to resurrect the previously discarded
electrochemical reduction process. This contribution describes
the preparation of 3-exomethylene-7(R)-glutaroylaminocepham-4-carboxylic acid 1(S)-oxide (10,1(S)-oxide) in almost quantitative yield by the electrochemical reduction of 3-acetoxymethyl-7(R)-glutaroylaminoceph-3-em-4-carboxylic acid 1(S)-oxide
(9,1(S)-oxide) using a high-surface area tin mesh cathode. The
new product has been shown (see Bernasconi, E.; Lee, J.; Sogli,
L.; Walker, D. Org. Process Res. Dev.
2002, 6, 169) to be a
superior new intermediate for the preparation of orally active
cephalosporins such as Ceftibuten.
“…After reviewing this literature, and determining the fermentation/extraction and chemical processing changes which would be required to commercialize a process scheme based on intermediate 6 or 8 we were dissuaded from pursuing such a route. In brief, as is the case in utilizing 4 and 5 , evaluation of the published chemical methods for converting 3-substituted cephalosporins to the desired 3-H cephalosporins from a cost standpoint revealed that we would need to undertake a great deal of exploratory work to even be in a position to determine which of the many raw chemical recipes from this research literature 10 might be improved, integrated, and developed to create an economically attractive process. In addition our evaluation indicated that a relatively large investment in new process equipment would be needed.…”
Analysis of several options for the synthesis of Ceftibuten from
cephalosporin C-derived starting materials led to the conclusion
that the most practical option, leading to the lowest costs, would
be realized by trying to resurrect the previously discarded
electrochemical reduction process. This contribution describes
the preparation of 3-exomethylene-7(R)-glutaroylaminocepham-4-carboxylic acid 1(S)-oxide (10,1(S)-oxide) in almost quantitative yield by the electrochemical reduction of 3-acetoxymethyl-7(R)-glutaroylaminoceph-3-em-4-carboxylic acid 1(S)-oxide
(9,1(S)-oxide) using a high-surface area tin mesh cathode. The
new product has been shown (see Bernasconi, E.; Lee, J.; Sogli,
L.; Walker, D. Org. Process Res. Dev.
2002, 6, 169) to be a
superior new intermediate for the preparation of orally active
cephalosporins such as Ceftibuten.
“…C 69,40 H 4.99 N 5.78 0 13,21 S 6,62% (484,57) Gef. ,, 69,47 ,,5,Ol ,,5,73 ,,13,26 ,,6,66% (C,H5)21; 7530 (s/3 CeH5).…”
mentioning
confidence: 99%
“…Die vcrsuchsweise Konfigurationszuordnung an C(4) bei 10a beruht auf Analogic [5]. Diese Tatsache ist beincrkenswcrt, da das d z :d3-Gleichgewicht bei Cephem-4-carbonslureestern in den nicisten uns bishcr bekannten Fallen eher auf Seiten des da-Isomeren licgt.…”
unclassified
“…Gef. ,, 56,58 ,,5,31 ,,9,46 ,,21,36 ,,. -a) Oxydation mit 2, Eine Losung von 0,900 g (2,58 mmol) 3-Hydroxymethyl-7~-phenylacrtamidoceph-2-em-4a-carbonsaure (3a) [l] in 50 ml abs.…”
Surnmavy. Benzhydrylic esters of 3-unsubstituted cephem-4-carboxylic acids of types 9 and 10 (Scheme 2) are prepared by decarbonylation of esters of 3-formylcephem compounds of type 2 with tris-triphenylphosphine-rhodium chloride. T h c preparation of the starting materials 2 and 5 , as wcll as of the nucleus 13 is described.Vor einiger Zeit beschrieben wir die Synthese von N-Acylderivaten der 7-Aminoceph-3-em-4-carbonsaure (13) ausgehend exper. Teil) . Bei der Dimethylsulfoxid/Saureanhydrid-Methode traten als Nebenprodukte die isomeren A2-Aldehyde vom Typ 5 und die von 1 abgeleiteten 0-Acylierungsprodukte auf, wahrend bei der Verwendung von Collins-Reagens als hauptsachliche Nebenprodukte die von 1 (nach Abspaltung der Benzhydrylgruppe) abgeleiteten Lactone nachgewiesen wurden.Problemloser verlief die Oxydation in der d2-Reihe. Hier konnten die freien Sauren, 2.B. die leicht zugangliche Saure 3a [7], eingesetzt werden, da diese keine Lactonisierungstendenz aufweisen. Sehr gute Ausbeuten an 4 a (Smp. 137-138') er-
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