SYNTHESIS OF POSITION-SPECIFIC TRITIUM-LABELED 20(S)-CAMPTOTHECIN, 9-AMINO-20(S)-CAMPTOTHECIN, AND 10,11-METHYLENEDIOXY-20(S)-CAMPTOTHECIN

The synthesis is given for three ring A tritiated camptothecin (CPT) a nalogs as biological probes in the study of the parent compounds which are of current widespread interest as potent anticancer agents. The s trategy of catalytic tritolysis of aryl halide bonds was employed, and thus the preparations of the requisite precursors 9-chloro-20(S)-CPT (9), 9-amino-10,12-dibromo-20(S)-CPT (14), and 9-chloro-10,11-methylen edioxy-20(S)-CPT (18) are given; catalytic tritiation of these respect ive precursors under polar, alkaline solvent conditions using palladiu m/carbon provides smooth conversion to [9-H-3]-20(S)-CPT (10), 9-amino -[10,12-H-3]-20(S)-CPT (15), and [9-H-3]-10,11-methylenedioxy-20(S)-CP T (19).