14-Fluoroanthracyclines. Novel syntheses and antitumor activity.

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Abstract
The 14-fluoroanthracyclines (5-10) carrying L-daunosamine, D-2-deoxyribose, or L-2-deoxy-fucose as their glycosidic sugar moieties were synthesized starting from (-)-7-deoxy-4-demethyoxy-daunomycinone ((R)-11a) or (-)-7-deoxydaunomycinone ((R)-11b). As key steps, the synthetic route features a novel fluorination reaction in which tetrabutylammonium fluoride is employed in the presence of a half equivalent of p-toluenesulfonic acid, and the previously explored glycosidation reaction in which trimethylsilyl trifluoromethanesulfonate is utilized as an activating reagent. In P388 in vitro tests, 5, 6, 9, and 10 exhibited prominent cytotoxicity comparable with that of adriamycin (1). Notable antitumor activity was also observed for 6 and 9 in P388 in vivo tests.