Chemical modification of an antitumor alkaloid camptothecin: synthesis and antitumor activity of 7-C-substituted camptothecins.
A radical substitution reaction of 20(S)-camptothecin (1) with methanol furnished 7-hydroxymethylcamptothecin (2). Reaction of 1 with primary alcohols higher than methanol gave 7-alkylcamptothecins (4), of which alkyl groups were one carbon less than the alcohols used and also 7-hydroxyalkylcamptothecins (5). For the preparation of 7-alkylcamptothecin (4), aldehydes were used as a radical source and several alkylated derivatives were synthesized. 7-Acyloxymethyl derivatives (6), 7-carbaldehyde (7), iminomethyl derivatives (10), acid (11), esters (12) and amides (13) were synthesized starting from 2. 7-Ethyl- (4b) and 7-propylcamptothecin (4c), acyloxymethyl compounds 6a, 6c and ethyl ester (12b) exhibited higher antitumor activity than 1 against L1210 in mice.
Sawada
S
S
Yakult Central Institute for Microbiological Research, Tokyo, Japan.
Nokata
K
K
Furuta
T
T
Yokokura
T
T
Miyasaka
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D007939:Leukemia L1210; D051379:Mice; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002166:Camptothecin