Synthesis and Antitumor Activity of 20(S)-Camptothecin Derivatives: A-Ring Modified and 7,10-Disubstituted Camntothecinslfl)

Abstract

20(*S)-Cainptothecin derivatives having nitro, amino, chloro, bromo, hydroxyl and methoxyl groups in the A-ring were synthesized. B-Ring hydrogenated camptothecin (2a) was converted into 10-hydroxycamptothecin (6e) by treatment with lead tetraacetate in trifiuoroacetic aicd. 10-Substituted derivatives (6) were obtained by a photoreaction of N-oxides (9). The cytotoxicity of the A-ring modified camptothecins was evaluated against KB cells in vitro and leukemia L1210 in mice. 7-Ethyl-10-hydroxycamptothecin (6i) was identified as a potential derivative for further modification. © 1991, The Pharmaceutical Society of Japan. All rights reserved.