PREPARATION OF CAMPTOTHECIN AND NOTHAPODYTINE DERIVATIVES

摘要

The invention concerns the preparation of nothapodytine or camptothecin derivatives which consists in causing 4-ethyl 2methyl hepta-2,4-dienoic acid act on a 3-aminomethyl 2-bromo quinoline derivative (III) wherein R1 and R2 are H or R1 is a halogen atom or alkyl, R2 is a O-CO-X radical as defined for the camptothecin derivatives; or R1 and R2 are defined for the known camptothecin derivatives or represent protected radicals or radicals easily convertible into the radicals R1 and R2, to obtain the quinoline derivative (IV); adding to the resulting quinoline derivative (2-methoxy carbonyl vinyl) tributyltin in the presence of a complex of palladium and triphenylarsin to obtain the quinoline derivative (V); cyclizing the resulting quinoline derivative to obtain the tetracyclic derivative (VI); then in subjecting said derivative to an ozonolysis followed by treatment with dimethyl sulphide to obtain the tetracyclic derivative (VII); saponification followed by decarboxylation in oxidising conditions of the resulting tetracyclic derivative to obtain the nothopodytine derivative (VIII); then optionally transforming the resulting derivative into a camptothecin derivative or into a mappicine derivative.