首页   按分类浏览 期刊浏览 卷期浏览 Synthesis of HR 916 K: An Efficient Route to the Pure Diastereomers of the 1‐(Pivaloylo...
Synthesis of HR 916 K: An Efficient Route to the Pure Diastereomers of the 1‐(Pivaloyloxy)ethyl Esters of Cephalosporins

 

作者: Elisabeth Defoßa,   Gerd Fischer,   Uwe Gerlach,   Rolf Hörlein,   Dieter Isert,   Norbert Krass,   Rudolf Lattrell,   Ulrich Stache,   Theo Wollmann,  

 

期刊: Liebigs Annalen  （WILEY Available online 1996）
卷期: Volume 1996, issue 11  

页码: 1743-1749

 

ISSN:0947-3440

 

年代: 1996

 

DOI:10.1002/jlac.199619961107

 

出版商: WILEY‐VCH Verlag

 

关键词: Cephalosporin, prodrug of;Antibiotics

 

数据来源: WILEY

 

摘要:

AbstractHR 916 K (5), the 1‐(S)‐(pivaloyloxy)ethyl prodrug ester of the cephalosporin cefdaloxime, exhibits a significantly higher oral bioavailability than the 1‐(R) diastereomer HR 916 J. An efficient synthesis of HR 916 K was developed. The separation of the diastereomers was achieved by precipitation of the 1‐(R)‐hydrochloride9followed by crystallization of the 1‐(S)‐amine10(de>96%). The 1‐(R) diastereomer9was recycled by acidic saponification or enzymatic cleavage to AMCA (7). The amine10was acylated with mercaptobenzothiazole thioesters or mixed anhydrides, prepared from carboxylic acids13and14, in almost quantitative yield. Deprotection of the oxime and formation of the tosylate proceeded in one step. Using thioester18, we obtained HR 916 K (5) from AMCA (

 

点击下载:  PDF (774KB)



返 回