Panipenem, CS-533, RS-533
帕尼培南Chemical Name: (5R,6S)-2-[1-Acetamidoylpyrrolidin-3(S)-ylthio]-6-[1(R)-hydroxyethyl]-2-carbapenem-3-carboxylic acid; (+)-(5R,6S)-3-[[(S)-1-Acetimidoylpyrrolidin-3-yl]thio]-6-[1(R)-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
CAS No. 87726-17-8
项目整合开发状态: Launched-1993
项目研究机构: Sankyo (Originator), Merck & Co. (Licensee)
合成路线:The reaction of 4-acetoxy-3-[(1-(tert-butyldimethylsilyloxy)ethyl]azetidin-2-one (I) with benzyl-3-pyrrolidinocrotonate (II) gives the enimine ester (III),which is hydrolyzed with HCl to the corresponding ketoester (IV).The cyclization of (IV),through the diazo compound (V) by means of rhodium acetate,yields the bicyclic ketoester (VI).The condensation of (VI) with 1-(4-nitrobenzyloxycarbonyl)-3-mercaptopyrrolidine (VII) affords the protected carbapenem compound (VIII),which is deprotected by hydrogenation with H2 over Pd/C in THF giving 6-(1-hydroxyethyl)-2-(pyrrolidin-3-ylthio)-1-carbapen-2-em-2-carboxylic acid (IX).Finally,this compound is condensed with ethyl acetimidate (X) in a phosphate buffer.
📌 参考资料/链接：
参考文献标题:RS-533
文献作者:Serradell,M.N.; Castar,J.
参考来源:Drugs Fut 1985,10(12),989
📄 详细内容
合成路线:The reaction of 4-acetoxy-3-[(1-(tert-butyldimethylsilyloxy)ethyl]azetidin-2-one (I) with benzyl-3-pyrrolidinocrotonate (II) gives the enimine ester (III),which is hydrolyzed with HCl to the corresponding ketoester (IV).The cyclization of (IV),through the diazo compound (V) by means of rhodium acetate,yields the bicyclic ketoester (VI).The condensation of (VI) with 1-(4-nitrobenzyloxycarbonyl)-3-mercaptopyrrolidine (VII) affords the protected carbapenem compound (VIII),which is deprotected by hydrogenation with H2 over Pd/C in THF giving 6-(1-hydroxyethyl)-2-(pyrrolidin-3-ylthio)-1-carbapen-2-em-2-carboxylic acid (IX).Finally,this compound is condensed with ethyl acetimidate (X) in a phosphate buffer.
参考文献标题:Synthesis and in vitro activity of a new carbapenem,RS-533
文献作者:Miyadera,T.; Sugimura,Y.; Hashimoto,T.; Tanaka,T.; Iino,K.; Shibata,T.; Sugawara,S.
参考来源:J Antibiot 1983,36(8),1034
产品链接: CAS No. 87726-17-8››