【药物名称】Rifalazil, ABI-1648, K-1648, PA-1648, KRM-1648
化学结构式(Chemical Structure):
参考文献No.12395
标题:3'-Hydroxybenzoxazinorifamycin deriv., process for preparing the same and antibacterial agent containing them
作者:Yamane, T.; Hashizume, T.; Yamashita, K.; Hosoe, K.; Kuze, F.; Watanabe, K. (Kaneka Corp.)
来源:EP 0366914; JP 1991007291; US 4983602
合成路线图解说明:

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.

参考文献No.202905
标题:Synthesis and biological activity of 3'-hydroxy-5'-aminobenzoxazinorifamycin derivatives
作者:Yamane, T.; Hashizume, T.; Yamashita, K.; Konishi, E.; Hosoe, K.; Hidaka, T.; Watanabe, K.; Kawaharada, H.; Yamamoto, T.; Kuze, F.
来源:Chem Pharm Bull 1993,41(1),148
合成路线图解说明:

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.

合成路线图解说明:

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.

Drug Information Express,Drug R&D,Chemical Database,Patent Search.
Copyright © 2006-2024 Drug Future. All rights reserved.Contact Us