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

Authors:
  • SMShun-Ichi Matsuoka
    Shun-Ichi Matsuoka
  • KNKen-Ichiro Nokata
    Ken-Ichiro Nokata
  • HNHiroshi Nagata
    Hiroshi Nagata
  • TFTomio Furuta
    Tomio Furuta
  • TYTeruo Yokokura
    Teruo Yokokura
  • TMTadashi Miyasaka
    Tadashi Miyasaka
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Abstract
20(S)-Camptothecin 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 trifluoroacetic acid. 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.