TOP-53
TOP-53双盐酸盐 2’-O-没食子酰基金丝桃甙 Chemical Name: [5R-(5alpha,5abeta,8aalpha,9beta)]-9-[2-[N-[2-(Dimethylamino)ethyl]-N-methylamino]ethyl]-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6-one dihydrochloride
CAS No. 147238-98-0, 148262-19-5 (free base)
项目整合开发状态: Phase I
项目研究机构: Taiho (Originator)
合成路线:The condensation of 4'-O-(benzyloxycarbonyl)-4'-demethylepipodophyllotoxin (I) with allyltrimethylsilane (II) by means of boron trifluoride ethearate in dichloromethane gives 4beta-allyl-4'-O-(benzyloxycarbonyl)-4'-demethyl-4-desoxypodophyllotoxin (III),which is oxidized with OsO4 and N-methylmorpholine (NMO) in acetone to the substituted acetaldehyde (IV).The reductocondensation of (IV) with N,N,N'-trimethylethylenediamine (V) by means of sodium cyanoborohydride and acetic acid in CHCl3 affords the protected final product (VI),which is finally hydrogenated with H2 over Pd/C in methanol.
📌 参考资料/链接：
参考文献标题:4-Desoxy-4-epipodophyllotoxin deriv.or pharmaceutically aceptable salt thereof
文献作者:Terada,T.; Fujimoto,K.; Nomura,M.; Yamashita,J.; Takeda,S.; Kobunai,T.; Yamaguchi,H.; Wierzba,K.(Taiho Pharmaceutical Co.,Ltd.)
参考来源:EP 0522173; JP 1993503298; WO 9212982
📄 详细内容
合成路线:The condensation of 4'-O-(benzyloxycarbonyl)-4'-demethylepipodophyllotoxin (I) with allyltrimethylsilane (II) by means of boron trifluoride ethearate in dichloromethane gives 4beta-allyl-4'-O-(benzyloxycarbonyl)-4'-demethyl-4-desoxypodophyllotoxin (III),which is oxidized with OsO4 and N-methylmorpholine (NMO) in acetone to the substituted acetaldehyde (IV).The reductocondensation of (IV) with N,N,N'-trimethylethylenediamine (V) by means of sodium cyanoborohydride and acetic acid in CHCl3 affords the protected final product (VI),which is finally hydrogenated with H2 over Pd/C in methanol.
参考文献标题:Antitumor agents.3.Synthesis and biological activity of 4beta-alkyl derivatives containing hydroxy,amino,and amido groups of 4'-O-demethyl-4-desoxypodophyllotoxin as antitumor agents
文献作者:Terada,T.; Fujimoto,K.; Nomura,M.; Yamashita,J.; Wierzba,K.; Yamazaki,R.; Shibata,J.; Sugimoto,Y.; Yamada,Y.; Kobunai,T.; et al.
参考来源:J Med Chem 1993,36(12),1689-99
合成路线:The condensation of 4'-O-(benzyloxycarbonyl)-4'-demethylepipodophyllotoxin (I) with allyltrimethylsilane (II) by means of boron trifluoride ethearate in dichloromethane gives 4beta-allyl-4'-O-(benzyloxycarbonyl)-4'-demethyl-4-desoxypodophyllotoxin (III),which is oxidized with OsO4 and N-methylmorpholine (NMO) in acetone to the substituted acetaldehyde (IV).The reductocondensation of (IV) with N,N,N'-trimethylethylenediamine (V) by means of sodium cyanoborohydride and acetic acid in CHCl3 affords the protected final product (VI),which is finally hydrogenated with H2 over Pd/C in methanol.
参考文献标题:TOP-53
文献作者:Leeson,P.A.; Castar,J.
参考来源:Drugs Fut 1996,21(11),1136
产品链接: CAS No. 147238-98-0›› 产品链接: CAS No.148262-19-5››