Vinblastine desacetyl

About 10 g of VLB (vincaleucoblastine or simply vinblastine) sulfate were converted by standard procedures to VLB free base. The free base, obtained as a residue after evaporation of the dried ethereal solvent, was dissolved in about 200 ml of anhydrous methanol. Anhydrous liquid ammonia (300 ml) was added, and the reaction mixture sealed and maintained at about 100°C for 60 hours. The reaction vessel was opened, and the contents removed and evaporated to dryness in vacuo. The resulting residue, containing 4-desacetyI VLB C-3 carboxamide, as shown by thin layer chromatography, were combined and the solvent evaporated therefrom in vacuo, yielding asa residue purified 4-desacetyl VLB C-3 carboxamide free base. The NMR and IR spectra of the solid free base confirmed the structure indicated. The free base showed a band in the infrared at 1,687 cm-1, characteristic of the amide function. The molecular weight of the free base determined by mass spectroscopy was 753 which is in agreement with theoretical value calculated for C43H55N5O7. 

Himes, R. H., Kersey, R. N., Heller-Bettinger, I., and Samson, F. E. (1976). Action of the vinca alkaloids vincristine, vinblastine, and desacetyl vinblastine amide on microtubules in vitro. Cancer Res. 36, 3798—3802. 

Desacetyl vinblastine amide, 1063 Desacetyl-lanatoside C, 517 Desacetylmetipranolol, 776 Desacetylrifampicin, 960 Desacetylthymoxamine, 1023 Desacetyl vinblastine, 1063 Desacort-Beta, 392 Desalkylflupenthixol, 628 Desalkylflurazepam, 631 Desalkylhydroxyflurazepam, 631 Desalkylnaloxone, 797 Desamethasone, 518 Deschlorobenzoylindomethacin, 682 Deseril, 775 Desemil, 775 Deserpidine, 515 Desethylchloroquine, 671... 

EC145 (A5), a folic acid conjugate of desacetyl vinblastine monohydrazide, represents a new generation of receptor-specific targeted chemotherapy and is undergoing Phase I anticancer clinical trials (19). Phase II trials for bladder and kidney cancers are underway with vinflunine (A6), a bifluorinated vinorelbine derivative (20, 21). 

The high toxicity24 33 34 and rather complex structure of vinblastine have limited the study of its metabolism. No metabolic studies in humans have been reported. All investigations to date have been made in rats using tritiated vinblastine. Except for trace amounts of desacetyl-vinblastine found27 in the blood of rats two hours after intraperitoneal injection, no metabolites have been identified. However, other unidentified metabolites have been isolated in small amounts26. No pharmacokinetic constants have been observed in the literature. 

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