Synthesis of enatiopure fluorine-containing taxoids and their use as anticancer agents as well as probes for biomedical problems

A series of fluorine-containing analogs of paclitaxel and docetaxel are synthesized through the coupling of (3R,4S)-1-acyl-β-lactams of high enantiomeric purity with various baccatin derivatives as the key step. Some taxoids bearing CF₃ or CF₂H at the C-3′ position are up to three orders of magnitude more porent than paclitaxel or doxorubin against human breast cancer cell lines, including those that are drug resistant. Metaboism studies show that fluorinated taxoid block the action of cytochrome P-450s. A combination of ¹⁹F and ¹H NMR analyses with molecular modeling has disclosed a previously unrecognized conformer that may be the first structure to be recognized by microtubles and the one tightly bound to the protein.