[New antitumor derivatives of vinblastine]

The alkaloids of Catharanthus roseus vincristine 1 and vinblastine 2 are widely used in the chemotherapy of cancer. Their nitro-derivatives have also antitumour activity [2]. The dinitro-derivatives 4, 6-9 were prepared for pharmacological investigation. Some new hydroxymethyl derivatives 12-14, 17-18, 23-24 of the antitumour indole-indoline alkaloids vinblastine 2 and leurosine 5 were synthetised in two different ways a) by the selective reduction of 2, 5 or deacetoxy-vinblastine 16, b) by the ferric chloride mediated coupling reaction of catharanthine 19 and the corresponding vindoline derivatives 21, 22. Synthetising 24 a new bisvindoline 25 was the main product. 13 and 14 showed cytotoxic activity for small cell lung cancer LXFS 650.