RESUMO
Objective: To optimize the synthesis process of deoxycholic acid according to the concept of the quality-based design(QBD)to ensure the safety and quality of the product. Methods： Based on a large number of literature and the referenced original patents, the plant sourced 9-hydroxyandrostenedione was selected and used as the starting material for the deoxycholic acid synthesis, in view of the advantages and disadvantages of each of the reported synthetic routes, and the synthesis process of the key intermediate 7 was investigated systematically with the particular attention. For the process impurities and optical isomer impurities generated in each reaction, the key parameters of the synthetic process were investigated and optimized in detail. At the same time, each step of post-reaction treatment and refining process was systematically investigated to provide the quality standard for the key intermediate 7. Results： Under the guidance of QBD, the reaction process parameters were optimized based on the single factor design experiments, by which the content of chiral isomers was reasonably controlled and the reaction yield was largely improved. Based on the results, a quality standard was designed for the key intermediate 7, and the reasonability and feasibility of the quality standard was proved by the successful synthesis of deoxychloic acid from 7 to obtain multiple batches of qualified deoxycholic acid samples. Conclusion： The whole process is stable and simply operable, and well matches the industrial requirement for the raw material deoxycholic acid synthesis.