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Complete assignment of 1 H and 13 C NMR spectra of vinflunine
Author(s) -
Ribet JeanPaul,
Zalavari Pascal,
Fahy Jacques,
Duflos Alain,
Beltran Thierry
Publication year - 2001
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/1097-458x(200101)39:1<43::aid-mrc786>3.0.co;2-g
Subject(s) - chemistry , heteronuclear molecule , two dimensional nuclear magnetic resonance spectroscopy , nuclear magnetic resonance spectroscopy , fluorine 19 nmr , nmr spectra database , vinca , nuclear overhauser effect , stereochemistry , computational chemistry , spectral line , physics , botany , astronomy , biology
A new family of fluorinated Vinca alkaloids was synthesized in superacidic media. Superacidic media were obtained by mixing a strong Brønsted acid, such as anhydrous hydrogen fluoride, with a strong Lewis acid, such as antimony pentafluoride. Thus vinflunine was obtained when vinorelbine was treated in HF–SbF 5 at −40 °C in the presence of a chlorinated solvent such as CH 2 Cl 2 , CHCl 3 or CCl 4 . Vinflunine was characterized by superior in vivo activity to vinorelbine in preclinical tumor models. The chemical structure of vinflunine was been examined using NMR spectrometry. Taking into account the complexity of the NMR spectra, the total assignment of the 1 H and the 13 C spectra required experiments using homonuclear ( 1 H– 1 H) and heteronuclear ( 1 H– 13 C) correlations such as gradient‐selected COSY (gs‐COSY), double‐quantum filtered COSY (DQFCOSY), heteronuclear multiple quantum‐correlation spectroscopy (HMQC) and heteronuclear multiple bond correlation spectroscopy (HMBC). We also undertook a comparative structural analysis between vinflunine base and vinflunine ditartrate in acetone solution. The conformation 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 diffraction study. The results indicated that the conformation in the solution state was analogous to that observed in the solid state. Copyright © 2001 John Wiley & Sons, Ltd.