Improvement On The Synthetic Process Of Key Intermediate Of Mifepristone

Mifepristone has been widely used as a progesterone receptor antagonist on clinic.The traditional synthetic route of mifepristione starting from 16-dehydropregnenolone acetate contains following deficiencies: long-synthetic steps and environmental pollution.In recent years,with the decreasing of dioscin resources,16-dehydropregnenolone acetate has become a high-cost material,which limited its pratical application.In this paper,we reported a new way to prepare the intermediate of mifepristone(3-acetoxy-5?-chloro-6?,19-oxidoandrostan-17-one)from an inexpensive raw material: 4-androstenedione(4-AD).The thesis consisted of two chapters:In the first chapter,the basic information of mifepristone was introduced,including pharmacokinetic,pharmacological effects,clinical application and total synthetic methods.In addition,the synthesis and applications of 4-AD and dehydroepiandrosterone(DHEA)were simply introduced.In the second chapter,three methods were designed to synthesize the key intermediate of mifepristone from 4-AD.Method 1: ?,?-unsaturated ketone was synthesized from 4-AD under the condition of t-BuOK,followed by epoxidation and ring opening reaction to obtain 6?-OH compound;Method 2: 3-keto function of 4-androstenedione was protected as ketal,compound 2b was obtained through hydrolysis reaction.Unfortunately,experimental results showed both method 1 and method 2 failed to give the target product.Method 3: initially,DHEA was prepared using 4-AD as raw material followed by esterification,acetalization,reduction and hydrolyzing.The compound 1 was obtained in three steps after esterification,hydroxychlorination and irradiation from DHEA.Through the experiment analysis and discussion,a route that have prospect of pratical application was proposed and the reaction conditions were also optimized.