Fremgangsmåde til fremstilling af 5'-nor-anhydrovinblastin-ditartrat ud fra planter af slægten Catharanthus

摘要

5' -nor-anhydrovinblastine ditartrate is synthesised from alkaloids extracted from plants of genus Catharanthus Roseus by way of a procedure which comprises the processing of the fresh plant so that the desired alkaloids undergo the least possible degradation; the use of an impure mixture of Vindoline and Catharanthine for the synthesis of anhydrovinblastine through the ferric ion catalyser; a method for anhydrovinblastine storage; purification and recycling of solvents; synthesis of crude 5' -nor-anhydrovinblastine in tandem without isolation of bromated intermediate; purification of crude 5' - nor-anhydrovinblastine by chromatography and crystallisation; and finally a method to obtain 5' -nor-anhydrovinblastine ditartrate which does not generate loss of active matter in order to obtain the desired purity. This results in a greater global yield, reduced process time, reduced use of solvents and a smaller number of purifications because it includes several reactions in single process steps. Thus, the new production process is more economical and efficient. The procedure may be divided in seven main stages, which are listed below: 1) grinding of the non-degraded Catharanthus plant 2) procurement of the total alkaloids of Catharanthus plant 3) procurement of the chromatographic fraction of Vindoline and Catharanthine 4) synthesis and purification of anhydrovinblastine 5) synthesis of 5' -nor-anhydrovinblastine 6) purification of crude 5' -nor-anhydrovinblastine 7) preparation of 5' -nor-anhydrovinblastine ditartrate