Complete assignment of H-1 and C-13 NMR spectra of vinflunine

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.