Deacetyl vinblastine

Activity of 4-Deacetyl vinblastine Amides against Gardner Lymphosarcoma in C3H Mice... 

Comparative Antitumor Activity of Selected 4-Deacetyl vinblastine Amides against Several Murine Tumor Models... 

Studies of the metabolism of vincristine and vinblastine have been complicated by chemical alterations of the drugs that occur during processing of samples for analysis. Extraction of these compounds under acidic conditions has been reported to minimize chemical degradation, and HPLC studies of the metabolism of vincristine indicate that microsomal preparations from mouse liver, but not those from human rhabdomyosarcoma tissue, convert vinblastine to 4-deacetyl vinblastine in vitro (38). 

Barnett CJ, Cullinan GJ, Gerzon K, Hoying RC, Jones WE, Newlon WM, Poore GA, Robison RL, Sweeney MJ, et al. Structure-activity relationships of dimeric Catharanthus alkaloids. 1. Deacetyl vinblastine amide vindesine sulfate. J. Med. Chem. 1978 21 88-96. 

The third alkaloid, pseudovincaleukoblastine diol, is isomeric with deacetyl-vinblastine, but the mass spectral evidence indicates that it is in fact a derivative of deacetoxyvinblastine. The remaining oxygen atom is contained in a secondary hydroxy-group (n.m.r. evidence) in the velbanamine portion of the molecule, and since the alkaloid and its acetate show similarities with vincadioline and its acetate, pseudovincaleukoblastine is formulated as (265) however, a carbinolamine structure (OH at C-3 ) cannot at present be firmly excluded. 

Figure 17 Separation of compounds using the optimum eluent composition achieved by factorial experimental design. Eluent hexane-dichloro methane-acetone-2-propanol (65 13 21 0.9, v/v) Compounds I, deacetyl-vinblastine II, vincristine III, N-demethyl-vinblastine IV, vinblastine V, deacetoxyvinblastine VI, leurosine the arrows show the unidentified peaks adjacent to vinblastine in the plant extract. (Reproduced by permission from Ref. 67.)...

Reaction of vinblastine (1) with excess ammonia in anhydrous methanol in a sealed pressure vessel at 100°C for 60 hr produces a mixture of products which gives, after chromatography on silica gel, 4-deacetylvin-blastine amide (vindesine, VDS, 59) and 4-deacetyl-18 -decarbomethoxy-vinblastine amide (60) in yields of 42 and 15%, respectively (53). A much improved preparation of vindesine (59) was realized by hydrazinolysis of... 

The compounds resulting from metabolism of the Vinca alkaloids are little characterized. The main hepatic metabolite of vinblastine, vincristine, vinorelbine and vinflunine seems to be, for each of the compounds, the respective 4-0-deacetyl alkaloid. Other metabolites have also been detected but only very seldom were structurally characterized [15, 191, 200-203],... 

Metabolic reactions in rats is deacetylation to give desacetylvinblastine which is the major metabolite of vinblastine ( 1,9). 

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