Flomoxef sodium, FMOX, 6315-S, Flumarin
氟氧头孢钠Chemical Name: (-)-(6R,7R)-7-[2-(Difluoromethylthio)acetamido]-7-methoxy-3-[[1-(2-hydroxyethyl)-1H-tetrazol-5-yl]thiomethyl]-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid sodium salt; 7beta-[(2-(Difluoromethylthio)acetamido]-7alpha-methoxy-3-[[1-(2-hydroxyethyl)-1H-tetrazol-5-yl]thiomethyl]-1-oxa-3-cephem-4-carboxylic acid sodium salt
CAS No. 92823-03-5, 92823-00-2 (free acid)
项目整合开发状态: Launched-1988
项目研究机构: Shionogi (Originator), ISF (Licensee)
合成路线:This compound can be prepared by the route shown in scheme:Reaction of chlorodifluoromethane (Freon 22) with ethyl thioglycolate (II) in the presence of ethanolic sodium ethoxide gives ethyl 2-(difluoro-methylthio)acetate (III),which is hydrolyzed with aqueous potassium hydroxide to yield 2-(difluoromethylthio)acetic acid (IV).Substitution of diphenylmethyl-7alpha-benzamido-3-chloromethyl-1-oxa-3-cephem-4-carboxylate (V),an important intermediate for production of latamoxef,with 1-(2-hydroxyethyl)-1H-tetrazole-5-thiol (VI) in the presence of sodium methoxide,followed by protection of the hydroxyl group by means of p-methylbenzyl chlorocarbonate (VII) and pyridine,gives diphenylmethyl 7alpha-benzamido-3-[[1-[2-(p-methylbenzyloxycarbonyloxy)ethyl-1H-tetrazol-5-yl]thiomethyl]-1-oxa-3-cephem-4-carboxylate (VIII).Methoxylation of (VIII) with tert-butylhypochlorite and lithium methoxide,followed by the conventional side-chain cleavage with phosphorus pentachloride pyridine methanol,affords diphenylmethyl 7beta-amino-7alpha-methoxy-3-[[1-[2-(p-methylbenzyloxycarbonyloxy)ethyl]-1H-tetrazol-5-yl]thiomethyl]-1-oxa-3-cephem-4-carboxylate (X).This amine (IX) is condensed with the acid (IV) by means of phosphoryl chloride and pyridine fo yield diphenyl-methyl 7beta[2-(dfluoromelhylthio)acetamido]-7alpha-methoxy-3-[[1-[2-(p-methylbenzyloxycarbonyloxy)ethyl]-1H-tetrazol-5 yl)thiomethyl]-1-oxa-3-cephem 4-carboxylate (X),which undergoes deprotection with stannic chloride and anisole,neutralization with aqueous sodium bicarbonate and lyophilization giving the sodium salt (XI).
📌 参考资料/链接：
参考文献标题:Flomoxef sodium
文献作者:Castar,J.; Serradell,M.N.
参考来源:Drugs Fut 1986,11(6),452
📄 详细内容
合成路线:This compound can be prepared by the route shown in scheme:Reaction of chlorodifluoromethane (Freon 22) with ethyl thioglycolate (II) in the presence of ethanolic sodium ethoxide gives ethyl 2-(difluoro-methylthio)acetate (III),which is hydrolyzed with aqueous potassium hydroxide to yield 2-(difluoromethylthio)acetic acid (IV).Substitution of diphenylmethyl-7alpha-benzamido-3-chloromethyl-1-oxa-3-cephem-4-carboxylate (V),an important intermediate for production of latamoxef,with 1-(2-hydroxyethyl)-1H-tetrazole-5-thiol (VI) in the presence of sodium methoxide,followed by protection of the hydroxyl group by means of p-methylbenzyl chlorocarbonate (VII) and pyridine,gives diphenylmethyl 7alpha-benzamido-3-[[1-[2-(p-methylbenzyloxycarbonyloxy)ethyl-1H-tetrazol-5-yl]thiomethyl]-1-oxa-3-cephem-4-carboxylate (VIII).Methoxylation of (VIII) with tert-butylhypochlorite and lithium methoxide,followed by the conventional side-chain cleavage with phosphorus pentachloride pyridine methanol,affords diphenylmethyl 7beta-amino-7alpha-methoxy-3-[[1-[2-(p-methylbenzyloxycarbonyloxy)ethyl]-1H-tetrazol-5-yl]thiomethyl]-1-oxa-3-cephem-4-carboxylate (X).This amine (IX) is condensed with the acid (IV) by means of phosphoryl chloride and pyridine fo yield diphenyl-methyl 7beta[2-(dfluoromelhylthio)acetamido]-7alpha-methoxy-3-[[1-[2-(p-methylbenzyloxycarbonyloxy)ethyl]-1H-tetrazol-5 yl)thiomethyl]-1-oxa-3-cephem 4-carboxylate (X),which undergoes deprotection with stannic chloride and anisole,neutralization with aqueous sodium bicarbonate and lyophilization giving the sodium salt (XI).
参考文献标题:Synthesis and antibacterial activity of 6315-S,a new member of the oxacephem antibiotic
文献作者:Tsuji,T.; Satoh,H.; Narisada,M.; Hamashima,Y.; Yoshida,T.
参考来源:J Antibiot 1984,38(4),466
产品链接: CAS No. 92823-03-5››