Cefclidin, E-1040
1-氨基双环[2.2.2]辛烷,4-(氨基羰基)-1-[[(6R,7R)-7-[[(2Z)-2-(5-氨基-1,2,4-噻二唑-3-基)-2-(甲氧基亚基)乙酰]-2-羧基-8-羟基-5-呻-1-阿氮双环[4.2.0]辛-2-烯-3-基]甲基]-,内盐Chemical Name: (6R,7R)-3-[(4-Carbamoyl-1-quinuclidinio)methyl]-7--[2-(5-amino-1,2,4-thiadiazol-3-yl)-(Z)-2-methoxy-iminoacetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate; (+)-1-[[(6R,7R)-7-[2-(5-Amino-1,2,4-thiadiazol-3-yl)glyoxylamido]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-4-carbamoylquinuclidinium hydroxide inner salt 7(2)-(Z)-(O-methyloxime)
CAS No. 105239-91-6
项目整合开发状态: Phase II
项目研究机构: Eisai (Originator)
合成路线:The reaction of 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-(methoxyimino)acetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid (I) with N-methyl-N-(trimethylsilyl)trifluoroacetamide and then with iodotrimethylsilane in dichloromethane gives the corresponding silylated 3-iodomethyl derivative (II),which is then treated with 4-carbamoylquinuclidine (III) in acetonitrile.
📌 参考资料/链接：
参考文献标题:Cephem cpds.having at the 3-position a (1,4-methylene-1-piperidinio)methyl group or a (1-quinuclidinio)methyl group
文献作者:Kamiya,T.; Machida,Y.; Negi,S.; Nomoto,S.; Saito,I.; Sugiyama,I.; Yamauchi,H.(Eisai Co.,Ltd.)
参考来源:AU 8652240; EP 0188255; ES 8703885; JP 1987030786; JP 1987123189; US 4748171; US 5010188
📄 详细内容
合成路线:The reaction of 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-(methoxyimino)acetamido]-3-acetoxymethyl-3-cephem-4-carboxylic acid (I) with N-methyl-N-(trimethylsilyl)trifluoroacetamide and then with iodotrimethylsilane in dichloromethane gives the corresponding silylated 3-iodomethyl derivative (II),which is then treated with 4-carbamoylquinuclidine (III) in acetonitrile.
参考文献标题:E-1040
文献作者:Prous,J.; Castar,J.
参考来源:Drugs Fut 1988,13(2),117
合成路线:A new synthesis for [14C]-E-1040 has been described:The cyclization of [14C]-labeled potassium thiocyanate (I) with 2-(N-chlorocarboxamidino)-2-(methoxyimino)acetic acid (II) in methanol by means of triethylamine gives 2-(2-aminothiazol-4-yl)-2(Z)-(methoxyimino)acetic acid (III),which is treated with PCl5 in dichloromethane,yielding the corresponding acyl chloride (IV).Finally,this compound is condensed with 7-amino-3-(4-carbamoylquinuclidinio-1-ylmethyl)-3-cephem-4-carboxylate (V) by means of sodium acetate in dichloromethane.
参考文献标题:Synthesis of (6R,7R)-7-[2-(5-amino-1,2,4-[5-C-14]thiadiazol-3-yl)-(Z)-2-methoxyiminoacetamido]-3-[(4-carbomoyl-1-quinuclidinio)methyl]ceph-3-em-4-carboxylate([C-14]E1040)
文献作者:Sugiyama,I.; Nomoto,S.; Mizuo,H.; Yamauchi,H.
参考来源:J Label Compd Radiopharm 1991,29(12),1309
合成路线:A new synthesis of [14C]-labeled E-1040 with the label in the quinuclidine ring has been reported:The reduction of [14C]-labeled bromoacetic acid (I) with borane-dimethyl sulfide complex in ethyl ether gives 2-bromoethanol (II),which is condensed with piperidine-4-carboxamide (III) by means of K2CO3 and KI in refluxing isopropanol,yielding the [14C]-labeled 1-(2-hydroxyethyl)piperidine-4-carboxamide (IV).The reaction of (IV) with SOCl2 in refluxing acetonitrile affords the 1-(2-chloroethyl)piperidine-4-carbonitrile (V),which is cyclized by means of lithium diisopropylamide in THF,giving the quinuclidine (VI).The hydrolysis of (VI) with sulfuric acid gives [14C]-labeled quinuclidine-4-carboxamide (VII),which is finally condensed with the 3-chloromethylcephalosporin (VIII) by means of Na in acetone and a treatment with trifluoroacetic acid.
参考文献标题:Synthesis of 14C-labelled cefclidin (E1040)
文献作者:Woolley,G.T.; Sugiyama,I.; Yamauchi,H.; Mizuo,H.
参考来源:J Label Compd Radiopharm 1992,31(9),663
产品链接: CAS No. 105239-91-6››