E-1010, ER-35786

Chemical Name: (1R,5S,6S)-6-[1(R)-Hydroxymethyl]-2-[2(S)-[1(R)-hydroxy-1-[pyrrolidin-3(R)-yl]methyl]pyrrolidin-4(S)-ylsulfanyl]-1-methyl-1-carba-2-penem-3-carboxylic acid monohydrochloride
CAS No. 186319-97-1
项目整合开发状态: Phase I
项目研究机构: Eisai (Originator)
合成路线:The thiol (II) has been obtained as follows:The aldehyde (V),which is synthesized from trans-4-hydroxy-L-proline in several steps (3),reacts with the lithium enolate of the pyrrolidone (IV) to afford the alcohol (VI) and its diastereomeric isomers.After purification on a silica gel column,reduction of (VI) by borane-dimethylsulfide in refluxing THF gives (VII).Removal of the amino protecting groups of (VII) by TFA,followed by reprotection with PNZ groups and then removal of the tert-butyldimethylsilyl group with Bu4NF gives the diol (VIII).Selective mesylation of (VIII),followed by reaction with potassium thioacetate,gives (IX),which is treated with aqueous 1 N NaOH in methanol to afford the thiol (II).
📌 参考资料/链接:
参考文献标题:2-(Substd.pyrrolidinylthio)carbapenem derivs
文献作者:Nakagawa,S.; Ohtake,N.; Nakano,F.; Yamada,K.; Ushijima,R.; Murase,S.; Fukatsu,H.(Banyu Pharmaceutical Co.,Ltd.)
参考来源:EP 0449191; JP 1992321688; US 5373002; US 5374720; US 5438054; WO 9114687

📄 详细内容


合成路线:The condensation of the enolphosphate (I) (1) and the thiol (II) in the presence of diisopropylethylamine gives the protected compound (III),which is deprotected by hydrogenolysis with H2 over Pd(OH)2 on carbon,purified by reverse-phase silica gel chromatography and treated with HCl to afford ER-35786 (2),as shown in Scheme 22662001a.

参考文献标题:ER-35786,a new antipseudomonal carbapenem: I.Synthesis and structure-activity relations of 2-substituted 1beta-methyl carbapenems
文献作者:Sato,N.; Sasho,M.; Kamada,A.; Suzuki,T.; Ashizawa,K.; Sugiyama,I.
参考来源:35th Intersci Conf Antimicrob Agents Chemother (Sept 17-20,San Francisco) 1995,Abst F151


合成路线:The condensation of the enolphosphate (I) (1) and the thiol (II) in the presence of diisopropylethylamine gives the protected compound (III),which is deprotected by hydrogenolysis with H2 over Pd(OH)2 on carbon,purified by reverse-phase silica gel chromatography and treated with HCl to afford ER-35786 (2),as shown in Scheme 22662001a.

合成路线:The thiol (II) has been obtained as follows:The aldehyde (V),which is synthesized from trans-4-hydroxy-L-proline in several steps (3),reacts with the lithium enolate of the pyrrolidone (IV) to afford the alcohol (VI) and its diastereomeric isomers.After purification on a silica gel column,reduction of (VI) by borane-dimethylsulfide in refluxing THF gives (VII).Removal of the amino protecting groups of (VII) by TFA,followed by reprotection with PNZ groups and then removal of the tert-butyldimethylsilyl group with Bu4NF gives the diol (VIII).Selective mesylation of (VIII),followed by reaction with potassium thioacetate,gives (IX),which is treated with aqueous 1 N NaOH in methanol to afford the thiol (II).

参考文献标题:ER-35786
文献作者:Sato,N.; Ohba,F.
参考来源:Drugs Fut 1996,21(4),361


合成路线:The condensation of the enolphosphate (I) (1) and the thiol (II) in the presence of diisopropylethylamine gives the protected compound (III),which is deprotected by hydrogenolysis with H2 over Pd(OH)2 on carbon,purified by reverse-phase silica gel chromatography and treated with HCl to afford ER-35786 (2),as shown in Scheme 22662001a.
参考文献标题:Crystalline 1-methyl-2-diphenylphosphoryloxy-carbapenem compounds
文献作者:Kaneda,S.; Hayasi,K.; Kumagai,T.
参考来源:JP 92330085


产品链接: CAS No. 186319-97-1››