Synthesis and biological evaluation of quinocarcin derivatives.
Cyanation of quinocarcin readily opened the oxazolidine ring to provide DX-52-1 (2), which was a key compound in the synthesis of quinocarcin derivatives. Various electrophilic reactions toward aromatic ring of DX-52-1 were examined, and 10-substituted (e.g., halogen, nitro, formyl, cyano, hydroxy, etc.) analogs were prepared. Dehydrocyanation of the derivatives could be achieved to reproduce the oxazolidine ring upon treatment with HCl or AgNO3. 10-Chloride 10 and 10-bromide 11 were the most promising among the derivatives prepared. Antitumor activity of 10 was extended to B-16 melanoma.
Saito
H
H
Kyowa Hakko Kogyo Co., Ltd., Tokyo Research Laboratories, Japan.
Kobayashi
S
S
Uosaki
Y
Y
Sato
A
A
Fujimoto
K
K
Miyoshi
K
K
Ashizawa
T
T
Morimoto
M
M
Hirata
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D007546:Isoquinolines / Q000138:chemical synthesis / Q000494:pharmacology; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains
D000903:Antibiotics, Antineoplastic; D007546:Isoquinolines; C038710:quinocarcin