【药物名称】E-1010, ER-35786
化学结构式(Chemical Structure):
参考文献No.15866
标题:2-(Substd. pyrrolidinylthio)carbapenem derivs
作者:Nakagawa, S.; Ohtake, N.; Nakano, F.; Yamada, K.; Ushijima, R.; Murase, S.; Fukatsu, H. (Banyu Pharmaceutical Co., Ltd.)
来源:EP 0449191; JP 1992321688; US 5373002; US 5374720; US 5438054; WO 9114687
合成路线图解说明:

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No.323043
标题:ER-35786, a new antipseudomonal carbapenem: I. Synthesis and structure-activity relations of 2-substituted 1beta-methyl carbapenems
作者:Sato, N.; Sasho, M.; Kamada, A.; Suzuki, T.; Ashizawa, K.; Sugiyama, I.
来源:35th Intersci Conf Antimicrob Agents Chemother (Sept 17-20, San Francisco) 1995,Abst F151
合成路线图解说明:

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No.353125
标题:ER-35786
作者:Sato, N.; Ohba, F.
来源:Drugs Fut 1996,21(4),361
合成路线图解说明:

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.

合成路线图解说明:

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No.900012
标题:Crystalline 1-methyl-2-diphenylphosphoryloxy-carbapenem compounds
作者:Kaneda, S.; Hayasi, K.; Kumagai, T.
来源:JP 92330085
合成路线图解说明:

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.

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