A new family of fluorinated Vinca alkaloids was synthesized in superacidic
media. Superacidic media were obtained by mixing a strong Bronsted acid, su
ch as anhydrous hydrogen fluoride, with a strong Lewis acid, such as antimo
ny pentafluoride. Thus vinflunine was obtained when vinorelbine was treated
in HF-SbF5 at -40 degreesC in the presence of a chlorinated solvent such a
s CH2Cl2, CHCl3 or CCl4. Vinflunine was characterized by superior in vivo a
ctivity to vinorelbine in preclinical tumor models. The chemical structure
of vinflunine was been examined using: NMR spectrometry. Taking into accoun
t the complexity of the NMR spectra, the total assignment of the H-1 and th
e C-13 spectra required experiments using homonuclear (H-1-H-1) and heteron
uclear (H-1-C-13) correlations such as gradient-selected COSY (gs-COSY), do
uble-quantum filtered COSY (DQFCOSY), heteronuclear multiple quantum-correl
ation spectroscopy (HMQC) and heteronuclear multiple bond correlation spect
roscopy (HMBC). We also undertook a comparative structural analysis between
vinflunine base and vinflunine ditartrate in acetone solution. The conform
ation of the vinflunine base molecule in acetone solution was studied with
a NOESY experiment. The structure of vinflunine was thus determined without
ambiguity, and its conformation was verified by a single-crystal x-ray dif
fraction study. The results indicated that the conformation in the solution
state was analogous to that observed in the solid state. Copyright (C) 200
1 John Wiley & Sons, Ltd.