F-910754

Chemical Name: N-[4-(beta-D-Glucopyranuronosyloxy)-3-nitrobenzyloxycarbonyl]daunomycin
项目整合开发状态: Preclinical
项目研究机构: Aventis Pharma (Originator), Dade Behring Marburg (Originator), Institut Curie (Originator)
合成路线:Ring opening of D-glucuronolactone (I) with NaOMe,followed by peracetylation and bromination of the resulting methyl uronate (II),afforded bromopyranose (III).Coupling of (III) with benzaldehyde (IV) using silver oxide in acetonitrile provided aldehyde (V),which was reduced with NaBH4 in the presence of silica gel in CHCl3-i-PrOH at 0 C to give benzyl alcohol (VI).Subsequent reaction with 4-nitrophenyl chloroformate (VII) in the presence of Et3N formed nitrophenyl carbonate (VIII) which,without purification,was coupled with doxorubicin (IX) in the presence of Et3N in DMF to give (X).

合成路线:Deacetylation of (X) on treatment with NaOMe in MeOH-DMF yielded methyl ester (XI),which was finally hydrolyzed with NaOH in H2O-THF at -10 C to furnish the target uronic acid.