Vinca alkaloids have been widely used in cancer chemotherapy for over 30 years. 1 Extensive chemistry research has led to several total syntheses, 2 and numerous derivatives have been evaluated, with the aim of improving the therapeutic potency of this class. 3 However, only four drugs are currently available worldwide, namely vinblastine (1a), vincristine (1b), a semisynthetic amide related to vinblastine, vindesine 4 (1c, Scheme 1), and vinorelbine (2, Navelbine).Vinorelbine (2) was obtained in two steps: (1) biomimetic coupling of the two precursor monomers, 5 catharanthine and vindoline, to form 3′,4′-anhydrovinblastine (3), and (2) C′ ring contraction of this intermediate 6 (Scheme 2).In our search for new and more potent vinorelbine derivatives, we were interested in an original chemical approach, which conceivably could induce dramatic changes in the skeleton of the molecule. We decided to investigate the reactivity of these highly functionalized compounds in superacid media. Superacids are able to induce modifications at nonactivated bonds, 7 and in these unusual conditions, indolines and indoles were found stable enough to react with various electrophiles. 8 The effects and reactivity of various electrophiles were investigated. Among these, chloromethanes (CH 2 Cl 2 , CHCl 3 , and CCl 4 ) act as superelectrophiles in HF-SbF 5 , the resulting cations CH 2 Cl + , CHCl 2 + , and CCl 3 + , respectively, exhibiting an extremely reactive hydride-abstracting power. 9Vinorelbine (2) was treated with CCl 4 in HF-SbF 5 at -40 °C. After workup, the main isolated product was identified as

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Capillary electrophoresis (CE) coupled to a capacitively coupled contactless conductivity detector (C 4 D) was used for the determination in a single analysis of a pharmaceutical drug and its counter-ion. Dual-opposite end injection (DOI) was used to introduce hydrodynamically the analytes at each end of the capillary. No modification of the commercial apparatus is required. After applying the voltage, the cations and anions migrate from each end of the capillary in opposite directions toward the detector placed near the cathode outlet. The electrophoretic conditions were initially developed with three test drugs (chlorpheniramine maleate, metoprolol tartrate, clomiphene citrate) and then applied to two Vinca alkaloids (catharanthine sulfate, vinorelbine ditartrate). The 10 mM histidine-50 mM acetic acid buffer (pH 4.1)-methanol 90:10 (v/v) electrolyte was suitable for the analysis of these high or medium mobile anions by CE-C 4 D due to its low conductivity background and high buffer capacity. Finally, the CE procedure developed was successfully validated for catharanthine sulfate. The method developed herein is fast (\10 min) and accurate (repeatability on migration time \ 0.6% and peak areas \ 1.3%, n = 6).

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