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) analogs as biological probes in the study of the parent compounds which are of current widespread interest as potent anticancer agents. The strategy 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-methylenedioxy-20(S)-CPT (18) are given; catalytic tritiation of these respective precursors under polar, alkaline solvent conditions using palladium/carbon provides smooth conversion to [9-3H]-20(S)-CPT (10), 9-amino-[10,12-3H]-20(S)-CPT (15), and [9-3H]-10,11-methylenedioxy-20(S)-CPT (19).