文献类型：期刊文献

英文题名：A Practical Synthesis of Cefcapene Pivoxil

作者：Jiang, Jian-An[2];Zhai, Jiao-Jiao[2];Yu, Xin-Hong[2];Teng, Xin[1];Ji, Ya-Fei[2]

机构：[1]E China Univ Sci & Technol, Sch Mat Sci & Engn, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China

年份：2012

卷号：44

期号：2

起止页码：207

外文期刊名：SYNTHESIS-STUTTGART

收录：;EI(收录号：20120314684270);WOS:【SCI-EXPANDED(收录号:WOS:000300198400006)，CCR-EXPANDED(收录号:WOS:000300198400006)】；

基金：We thank the National Natural Science Foundation of China (Project No. 21176074) and Shandong Haoyuan Co. Ltd. for financial support.

语种：英文

外文关键词：antibiotics; cephalosporins; cefcapene pivoxil; 7-ACA; carbamylation; semisynthesis

摘要：Cefcapene pivoxil monohydrochloride monohydrate, a broad spectrum third-generation cephalosporin for oral administration, was prepared by reacting three centers of 7 beta-amino-3-(hydroxymethyl)cephalosporinic acid (7-HACA), derived from 7 beta-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 diiso-propylamine 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.