- A practical synthesis of cefcapene pivoxil
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Cefcapene pivoxil monohydrochloride monohydrate, a broad spectrum third-generation cephalosporin for oral administration, was prepared by reacting three centers of 7-amino-3-(hydroxymethyl)cephalosporinic acid (7-HACA), derived from 7-aminocephalosporanic acid. The coupling of 7-HACA and (Z)-2-[2-(Boc-amino)thiazol-4-yl]pent-2-enoic acid, followed by carbamylation with chlorosulfonyl isocyanate, and precipitation with diisopropylamine gave the key intermediate, in which thiazole side chain and carbamoyl group had been introduced into the 7-amino and 3-hydroxymethyl groups of 7-HACA, respectively, in a continuous procedure. Afterwards, the intermediate was esterified with pivaloyloxymethyl iodide to complete the modification of the C4 carboxy group affording Boc-cefcapene pivoxil, from which the desired product was finally obtained by an economical Boc removal and successive formation of the hydrochloride in 36% overall yield on a decagram scale. This synthesis promises an easy entry to cefcapene pivoxil monohydrochloride monohydrate with convenient manipulation, simple isolation, and good yields; it is of potential value for production on an industrial scale. Georg Thieme Verlag Stuttgart · New York.
- Jiang, Jian-An,Zhai, Jiao-Jiao,Yu, Xin-Hong,Teng, Xin,Ji, Ya-Fei
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- AN IMPROVED PROCESS FOR THE PREPARATION OF CEPHALOSPORIN ANTIBIOTIC
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The present invention provides a process for the preparation of the compound of formula (I) and its salt and esters. More particularly, this present invention relates to an improved process for the preparation Cefcapene of formula (I) and its salt and esters.
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Page/Page column 11
(2009/01/23)
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- Synthesis and structure-activity relationships of 7β-[(Z)-2-(2-aminothiazol-4-yl)-3-(substituted)-2- propenoyl-amino]-3-cephems with C-3 substitutions
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Synthesis and biological activity of a series of 7β-[(Z)-2-(2-aminothiazol-4-yl)-3-(substituted)-2- propenoylamino]-3-cephem-4-carboxylic acids with C-3 substitutions and their pivaloyloxymethyl esters are described. These acid compounds exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria. Pivaloyloxymethyl esters of selected compounds in this series were found to be well absorbed from small intestine in mice. Pivaloyloxymethyl 7β-[(Z)-2-(2-aminothiazol-4-yl)-2-pentenoylamino]-3- carbamoyloxymethyl-3-cephem-4-carboxyiate hydrochloride hydrate (S-1108) was finally selected as the candidate for clinical evaluation.
- Ishikura,Kuboto,Minami,Hamashima,Nakashimizu,Motokawa,Kimura,Miwa,Yoshida
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p. 466 - 476
(2007/10/02)
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