Cilastatin sodium, Cilastatino, MK-791, L-642957
西司他丁钠 西司他丁 Chemical Name: [R-[R*,S*(Z)]]-7-[(2-Amino-2-carboxyethyl)thio]-2-[[(2,2-dimethylcyclopropyl)carbonyl]amino]-2-heptenoic acid monosodium salt
CAS No. 81129-83-1, 82009-34-5 (free acid)
项目整合开发状态: Launched-1985
项目研究机构: Merck & Co. (Originator)
合成路线:The alkylation of ethyl 1,3-dithiane-2-carboxylate (I) with 1,5-dibromopentane (II) by means of NaH in DMF gives ethyl 2-(5-bromopentyl)-1,3-dithiane-2-carboxylate (III),which is treated with NBS in acetonitrile water to open the dithiane ring yielding ethyl 7-bromo-2-oxoheptanoate (IV).Hydrolysis of the ester group of (IV) with 50% HBr affords 7-bromo-2-oxoheptanoic acid (V),which is condensed with 2,2-dimethylcyclopropanecarboxamide (VI) in refluxing toluene giving 7-bromo-2-(2,2-dimethycyclopropanecarboxamido)-2-octenoic acid (VII).Finally,this compound is condensed with L-cysteine (VIII) by means of NaOH in water.
📌 参考资料/链接：
参考文献标题:2-(Cyclopropanecarboxamido)-alkenoic acids,their esters and salts,and antibacterial compositions comprising the same a thiennamycin-type compound
文献作者:Graham,D.W.; Rogers,E.F.; Kahan,F.M.(Merck & Co.,Inc.)
参考来源:EP 0048301
📄 详细内容
合成路线:The alkylation of ethyl 1,3-dithiane-2-carboxylate (I) with 1,5-dibromopentane (II) by means of NaH in DMF gives ethyl 2-(5-bromopentyl)-1,3-dithiane-2-carboxylate (III),which is treated with NBS in acetonitrile water to open the dithiane ring yielding ethyl 7-bromo-2-oxoheptanoate (IV).Hydrolysis of the ester group of (IV) with 50% HBr affords 7-bromo-2-oxoheptanoic acid (V),which is condensed with 2,2-dimethylcyclopropanecarboxamide (VI) in refluxing toluene giving 7-bromo-2-(2,2-dimethycyclopropanecarboxamido)-2-octenoic acid (VII).Finally,this compound is condensed with L-cysteine (VIII) by means of NaOH in water.
参考文献标题:Cilastatin
文献作者:Castar,J.; Serradell,M.N.
参考来源:Drugs Fut 1984,9(5),320
合成路线:The condensation of 7-chloro-2-oxoheptanoic acid ethyl ester (I) with (S)-2,2-dimethylcyclopropanecarboxamide (II) by means of TsOH in refluxing toluene gives (S)-7-chloro-2-(2,2-dimethylcyclopropanecarboxamido)-2-heptenoic acid ethyl ester (III),which is hydrolyzed in aq.NaOH to yield the corresponding carboxylic acid (IV).Finally,this compound is condensed with (R)-cysteine (V) by means of NaOH in water to afford the target Cilastatino.
参考文献标题:Process for the preparation of cilastatin
文献作者:Tyagi,O.D.; Kumar,Y.; Srivastava,T.K.(Ranbaxy Laboratories Ltd.)
参考来源:WO 03018544
产品链接: CAS No. 81129-83-1›› 产品链接: CAS No.82009-34-5››