Synthesis of antitumor-active 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl)-daunomycinone and -adriamycinone.
The title compounds (17 and 23) were prepared by coupling 3,4-di-O-acetyl-2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl bromide (15) with daunomycinone. The key step in the preparation of 15 was the epoxide-ring opening of methyl 2,3-anhydro-4-O-benzyl-6-deoxy-alpha-L-gulopyranoside with KHF2 in ethylene glycol, whereupon 2-fluoro-alpha-L-idopyranoside was obtained. Compounds 17 and 23 showed strong antitumor activity.
Ok
K
K
Institute of Bioorganic Chemistry, Kawasaki, Japan.
Takagi
Y
Y
Tsuchiya
T
T
Umezawa
S
S
Umezawa
H
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use / Q000633:toxicity; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use / Q000633:toxicity; D007202:Indicators and Reagents; D007939:Leukemia L1210 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009904:Optical Rotation; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D007202:Indicators and Reagents; C049732:7-O-(2,6-dideoxy-2-fluorotalopyranose)adriamycinone; C049731:7-O-(2,6-dideoxy-2-fluorotalopyranosyl)daunomycinone; D004317:Doxorubicin; D003630:Daunorubicin