Synthesis of novel 3'-trifluoromethyl taxoids through effective kinetic resolution of racemic 4-CF₃-β-lactams with baccatins

The coupling of racemic 1-(t)Boc-4-CF₃-β-lactams with various C-10 modified baccatins has resulted in CF₃-taxoids with diastereoselectivities ranging from 9:1 to one single isomer. The observed high diastereoselectivity is ascribed to the highly efficient enantiomer-differentiation by the enantiopure lithium alkoxide of a baccatin III in the coupling reaction with a racemic l-(t)Boc-β-Mactam. These novel CF₃-taxoids have also been shown to exhibit significant increases in activity against various cancer cell lines compared to either paclitaxel or docetaxel. In addition, the first asymmetric synthesis of a CF₃-β-lactam via chiral ester enolate-imine cyclocondensation was performed with 50% enantioselectivity.