Chemical modification of antitumor alkaloids, 20(S)-camptothecin and 7-ethylcamptothecin: reaction of the E-lactone ring portion with hydrazine hydrate.
The structure of the N-amino pyridone (4a) obtained by the reaction of camptothecin (1a) with hydrazine was determined by X-ray crystallography. A mixture of 7-ethylcamptothecin (1b) and hydrazine hydrate was stirred at room temperature, and the hydrazide (2b) was isolated as its diacetate 2c. Treatment of the 17-O-acetyl amide (5a) with hydrazine gave 1b (74% yield) and the N-amino lactam 6 (11% yield). Compounds with bulky acyl groups, 5c--e, gave 6 in modest yields. The N-amino lactam 6 was smoothly dehydrated into the pyridone 4d by refluxing in hydrazine hydrate.
Yaegashi
T
T
Yakult Central Institute for Microbiological Research, Tokyo, Japan.
Sawada
S
S
Furuta
T
T
Yokokura
T
T
Yamaguchi
K
K
Miyasaka
T
T
D000818:Animals; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D005260:Female; D006834:Hydrazines / Q000737:chemistry; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice
D006834:Hydrazines; C029424:hydrazine; D002166:Camptothecin