Synthesis Of Deoxycholic Acid And Study On Key Intermediates

Purpose:Deoxycholic acid injection?brand name:Belkyra?was developed by Kessela Biopharmaceutical Co.,Ltd.and approved for marketing on April 29,2015.It is used to improve adult submandibular related fat with moderate to severe contour protrusion or excessive facial plump Drug.Its active ingredient is deoxycholic acid.The chemical name is 3?,12?-dihydroxy-5?-cholanoic acid.It is an injectable cell lysis drug.When injected into body tissues,this product can destroy the cell membrane and cause cell lysis.At present,deoxycholic acid injection has not been listed in China.Only approved the application of chemical drug category 3.1 clinical trial declared by Nanjing Nuorite Medical Technology Co.,Ltd.and the application of chemical drug category 5.1 clinical trial application of the original research Eljian Information Consulting Co.,Ltd.It has great development prospects.From the perspective of drug safety,the FDA only approves deoxycholic acid of non-animal origin for the development of injections.Therefore,the synthesis process of deoxycholic acid is a key step in the commercial development of this drug.This paper mainly studies the method of industrial synthesis of deoxycholic acid.Method:Based on consulting a large number of documents and referring to original research patents,the advantages and disadvantages of each synthetic route are compared.The plant-derived 9-hydroxyandrostenedione was selected as the starting material to produce deoxycholic acid through elimination,condensation,hydrogenation,reduction,esterification,and oxidation.The thesis optimizes the preparation process of key intermediates in the synthesis process.Which provides a theoretical basis for the formulation of quality standards,at the same time,a systematic study of each step of post-treatment and exquisite process is carried out.Results and Discussion:The structure of the synthesized compound was confirmed by ¹H NMR and ¹³C NMR.The crystal form of deoxycholic acid was determined.The whole process is stable and operable,and can fully meet the requirements of industrial production.The total yield of the six-step reaction is 30%,which lays the foundation for the synthesis of the raw material drug deoxycholic acid.Qualified deoxycholic acid samples were obtained through multiple batches,proving the rationality and feasibility of the entire synthetic route and the DOA-H6 quality standard.