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【结 构 式】 
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【分子编号】55053 【品名】benzhydryl (6R,7R)-3-{[5-chloro-2-(2,4-dichlorophenoxy)phenoxy]methyl}-8-oxo-7-{[2-(2-thienyl)acetyl]amino}-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 【CA登记号】 |
【 分 子 式 】C39H29Cl3N2O6S2 【 分 子 量 】792.15924 【元素组成】C 59.13% H 3.69% Cl 13.43% N 3.54% O 12.12% S 8.1% |
合成路线1
该中间体在本合成路线中的序号：(VI)Acylation of 7-aminocephalosporanic acid (I) with 2-thienyleacetyl chloride (II) in the presence of NaOH led to amide (III). The carboxylate group of (III) was then protected as the corresponding benzhydryl ester (IV) upon treatment with diphenyldiazomethane. Mitsunobu coupling of the hydroxymethyl cephem (IV) with triclosan (V), with partial double-bond isomerization, gave rise to a mixture of the desired delta-3 ether (VI) and its delta-2 isomer (VII), which were separated by repeated column chromatography. Isomerization was minimized by conducting the reaction at -20 C. Finally, removal of the benzhydryl ester group of (VI) was accomplished by treatment with trifluoroacetic acid in the presence of anisole.
| 【1】 Li, Q.; et al.; NB2001, a novel antibacterial agent with broad-specrum activity and enhanced potency against beta-lactamase-producing strains. Antimicrob Agents Chemother 2002, 46, 5, 1262. |
| 【2】 Lobl, T.J.; Chan, M.F.; Li, Q.; Doppalapudi, V.R.; Hixon, M.S.; Castillo, R. (NewBiotics, Inc.); Improved beta-lactam antibiotics. WO 0183492 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 22747 | (6R,7R)-3-[(acetoxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C10H12N2O5S | 详情 | 详情 | |
| (II) | 15673 | 2-(2-thienyl)acetyl chloride; 2-Thiopheneacetyl chloride | 39098-97-0 | C6H5ClOS | 详情 | 详情 |
| (III) | 55051 | (6R,7R)-3-(hydroxymethyl)-8-oxo-7-{[2-(2-thienyl)acetyl]amino}-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C14H14N2O5S2 | 详情 | 详情 | |
| (IV) | 39801 | benzhydryl (6R,7R)-3-(hydroxymethyl)-8-oxo-7-[[2-(2-thienyl)acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C27H24N2O5S2 | 详情 | 详情 | |
| (V) | 55052 | 2,4,4'-Trichloro-2'-hydroxydiphenyl ether; Triclosan | 3380-34-5 | C12H7Cl3O2 | 详情 | 详情 |
| (VI) | 55053 | benzhydryl (6R,7R)-3-{[5-chloro-2-(2,4-dichlorophenoxy)phenoxy]methyl}-8-oxo-7-{[2-(2-thienyl)acetyl]amino}-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | C39H29Cl3N2O6S2 | 详情 | 详情 | |
| (VII) | 55054 | benzhydryl (6R,7R)-3-{[5-chloro-2-(2,4-dichlorophenoxy)phenoxy]methyl}-8-oxo-7-{[2-(2-thienyl)acetyl]amino}-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylate | C39H29Cl3N2O6S2 | 详情 | 详情 |