Rifalazil, ABI-1648, K-1648, PA-1648, KRM-1648
利福拉齐Chemical Name: (2S,16Z,18E,20S,21S,22R,23R,24R,25S,26R,27S,28E)-25-Acetoxy-5,12,21,23-tetrahydroxy-27-methoxy-2,4,16,20,22,24,26-heptamethyl-10-[4-(2-methylpropyl)piperazin-1-yl]-2,7-(epoxypentadeca-1,11,13-trienimino)-1,2-dihydro-6H-benzofuro[4,5-a]phenoxazine-1,6,15-trione
CAS No. 129791-92-0
项目整合开发状态: Phase II
项目研究机构: Kaneka (Originator), ActivBiotics (Licensee), DepoMed (Codevelopment)
合成路线:The benzoxazinorifamycin (III) was obtained by oxidative condensation of rifamycin S (I) with 2-aminoresorcinol (II).1-Isobutylpiperazine (V),prepared by alkylation of piperazine (IV) with isobutyl bromide,was then coupled to the benzoxazine ring of (III) in the presence of MnO2 as the oxidant to afford the target piperazinyl derivative.In an improved procedure,2-aminoresorcinol (II) was protected as the mono-silyl ether (VI) and subsequently coupled to rifamycin S (I) in the presence of MnO2,yielding (VII).Oxidative coupling of the benzoxazino derivative (VII) with 1-isobutylpiperazine (V) proceeded with simultaneous desilylation to furnish the title compound.
📌 参考资料/链接：
参考文献标题:3'-Hydroxybenzoxazinorifamycin deriv.,process for preparing the same and antibacterial agent containing them
文献作者:Yamane,T.; Hashizume,T.; Yamashita,K.; Hosoe,K.; Kuze,F.; Watanabe,K.(Kaneka Corp.)
参考来源:EP 0366914; JP 1991007291; US 4983602
📄 详细内容
合成路线:The benzoxazinorifamycin (III) was obtained by oxidative condensation of rifamycin S (I) with 2-aminoresorcinol (II).1-Isobutylpiperazine (V),prepared by alkylation of piperazine (IV) with isobutyl bromide,was then coupled to the benzoxazine ring of (III) in the presence of MnO2 as the oxidant to afford the target piperazinyl derivative.In an improved procedure,2-aminoresorcinol (II) was protected as the mono-silyl ether (VI) and subsequently coupled to rifamycin S (I) in the presence of MnO2,yielding (VII).Oxidative coupling of the benzoxazino derivative (VII) with 1-isobutylpiperazine (V) proceeded with simultaneous desilylation to furnish the title compound.
合成路线:The mono-silylation of 2-aminoresorcinol (I) by means of tert-butyldimethylsilyl chloride and triethylamine yields silyl ether (II).Condensation of rifamycin S (III) with aminophenol (II),followed by oxidative treatment with MnO2 produces the benzoxazinorifamycin derivative (IV).Addition of N-propyl piperazine (V) to (IV) in the presence of MnO2 leads to the target piperazinyl benzoxazinorifamycin.
参考文献标题:Synthesis and biological activity of 3'-hydroxy-5'-aminobenzoxazinorifamycin derivatives
文献作者:Yamane,T.; Hashizume,T.; Yamashita,K.; Konishi,E.; Hosoe,K.; Hidaka,T.; Watanabe,K.; Kawaharada,H.; Yamamoto,T.; Kuze,F.
参考来源:Chem Pharm Bull 1993,41(1),148
产品链接: CAS No. 129791-92-0››