Synthesis of Anhydrovinblastine by Response Surface Methodology

Abstract

Anhydrovinblastine is the crucial intermediate of synthesizes vinorelbine and vinflunine, because of its complicated and difficult synthesizing processes, the yields of both preparation and synthesis are not high enough. Aiming at optimization of this process, experiment factors and levels were firstly selected by previously tests. According to the Box-Benhnken design principles, the method of response surface method with 3 factors and 3 levels was adopted. The factors influencing the technological parameters were determined by means of regression analysis. Response surface were finally graphed with the yield as the response value. The synthetic conditions are optimized are determined as follows: The vinblastine is dissolved in DMF and the concentration is 15 mmol/L; the reaction reagent is SOCl₂ and the stoichiometric proportions between reagent with vinblastine could be 50:1; the reaction temperature is 5 ºC and the duration is 12 h. The yield of anhydrovinblastine reaches 65.80 %.