新产品编号:1305659
Chemical Name: (1R,5S,6S)-2-[1,1-Dimethyl-2(S)-(piperazin-1-ylcarbonyl)pyrrolidinium-4(S)-ylsulfanyl]-6-[1(R)-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate hydrochloride
项目整合开发状态: Preclinical
项目研究机构: Sankyo (Originator)
合成路线:Mercaptoproline derivative (I) was condensed with protected piperazine (II) via activation with carbonyl diimidazole to afford amide (III).The 4-methoxybenzyl group of (III) was then removed with trifluoromethanesulfonic acid in the presence of anisole and trifluoroacetic acid,and the resulting mercaptan (IV) was condensed with carbapenem phosphate (VI),(prepared from ketone (V) and diphenylphosphorochloridate),to afford thioether (VII).N-Methylation was carried out using methyl fluorosulfonate to yield quaternary ammonium salt (VIII).Finally,the 4-nitrobenzyl ester and carbamate groups of (VIII) were eliminated by hydrogenation in the presence of Pd/C,and the target product was isolated by ion-exchange chromatography.
合成路线:Mercaptoproline derivative (I) was condensed with N-(carbamoylmethyl)homopiperazine (II) via activation with carbonyl diimidazole to afford amide (III).The 4-methoxybenzyl group of (III) was then removed with trifluoromethanesulfonic acid in the presence of anisole and trifluoroacetic acid,and the resulting mercaptan (IV) was condensed with carbapenem phosphate (VI),(prepared from ketone (V) and diphenylphosphorochloridate),to afford thioether (VII).N-Methylation of (VII) was carried out using methyl fluorosulfonate to yield quaternary ammonium salt (VIII).Finally,the 4-nitrobenzyl ester and carbamate groups of (VIII) were eliminated by hydrogenation in the presence of Pd/C,and the target product was isolated by ion-exchange chromatography.
📌 参考资料/链接：
参考文献标题:Carbapenem derivs.having antibiotic activity,their preparation and their use
文献作者:Kawamoto,I.; Miyauchi,M.; Nakayama,E.; Endo,R.; Ohya,S.; Utsui,Y.(Sankyo Co.,Ltd.)
参考来源:EP 0443883; JP 1992211083; US 5310735
📄 详细内容
合成路线:Mercaptoproline derivative (I) was condensed with protected piperazine (II) via activation with carbonyl diimidazole to afford amide (III).The 4-methoxybenzyl group of (III) was then removed with trifluoromethanesulfonic acid in the presence of anisole and trifluoroacetic acid,and the resulting mercaptan (IV) was condensed with carbapenem phosphate (VI),(prepared from ketone (V) and diphenylphosphorochloridate),to afford thioether (VII).N-Methylation was carried out using methyl fluorosulfonate to yield quaternary ammonium salt (VIII).Finally,the 4-nitrobenzyl ester and carbamate groups of (VIII) were eliminated by hydrogenation in the presence of Pd/C,and the target product was isolated by ion-exchange chromatography.
合成路线:Mercaptoproline derivative (I) was condensed with N-(carbamoylmethyl)homopiperazine (II) via activation with carbonyl diimidazole to afford amide (III).The 4-methoxybenzyl group of (III) was then removed with trifluoromethanesulfonic acid in the presence of anisole and trifluoroacetic acid,and the resulting mercaptan (IV) was condensed with carbapenem phosphate (VI),(prepared from ketone (V) and diphenylphosphorochloridate),to afford thioether (VII).N-Methylation of (VII) was carried out using methyl fluorosulfonate to yield quaternary ammonium salt (VIII).Finally,the 4-nitrobenzyl ester and carbamate groups of (VIII) were eliminated by hydrogenation in the presence of Pd/C,and the target product was isolated by ion-exchange chromatography.
参考文献标题:Synthesis and structure-activity relationships of 1beta-methylcarbapenems with quaternary ammonium side chains
文献作者:Ishikawa,K.; Kojima,K.; Miyauchi,M.; Endo,R.; Yasuda,H.; Kawamoto,I.
参考来源:J Antibiot 1998,51(8),757