194468-36-5

White Solid

Semisynthetic Vinca alkaloid with microtubule destabilizing and antiangiogenic activity; derivative of Vinorelbine. Antineoplastic

Vinflunine is a semisynthetic Vinca alkaloid with microtubule destabilizing and antiangiogenic activity. Vinflunine is a derivative of Vinorelbine. Vinflunine is used as an antineoplastic.

Vinflunine ditartrate is a second generation difluorinated analog of the naturally-occuring substance vinorelbine and it is approved for the treatment of non-small cell lung cancer, metastatic breast cancer and ovarian cancer. Vinflunine, a tubulin polymerization inhibitor, belongs to the vinca alkaloid class of anti-cancer agents. Introduction of the difluoro group of vinflunine dramatically improved antitumor activity of the parent vinorelbine structure. Vinflunine was discovered by Pierre Fabre Laboratories and in 2004 was licensed to Bristol-Myers Squibb for development and commercialization. In 2007, the rights to venflunine were returned to Pierre Fabre which completed its development.

Vinflunine can be prepared directly from vinorelbine (155) through the use of superacid chemistry. Reaction of 155 with antimony pentaflouride in hydrofluoric acid and Nbromosuccinimide followed by treatment with two equivalents of tartaric acid produced vinflunine ditartrate (XV) in 25% yield. An alternative synthesis of vinflunine was realized through reaction of vinblastine or 3?ˉ,4?ˉ-dihydrovinblastine (156) with antimony pentaflouride and hydrofluoric acid in chloroform to give the difluoro alkaloid 157 in 40% yield Ring contraction was effected by reaction with trifluoroacetic acid and N-bromosuccinimide followed by aqueous sodium bicarbonate and silver tetrafluoroborate to give vinflunine in 88% yield. Vinflunine ditartrate (XV) was prepared by treating a solution of vinflunine in toluene with two equivalents of tartaric acid.