Study On The Synthesis Of 3,16-androstenediones

Steroid compounds are a large group of chemical substances widely present in animals and plants.Many organisms can synthesize steroid compounds,which play an important role in many life activities.Steroid drugs have strong physiological activity and are clinically used in the treatment of various diseases.However,people's long-term use of steroid drugs has gradually revealed the human body's resistance to steroid drugs.At the same time,the toxic and side effects of steroid drugs themselves also need to arouse people's attention.How to reduce the resistance and toxicity of steroidal drugs and improve the activity of steroidal drugs to be treated is an urgent problem to be solved at present.The steroidal compounds androsta-4(5),14(15)-diene-3,16-dione and12?-hydroxyandrosta-4(5),14(15)-diene-3,16-dione shows high cell proliferation inhibitory activity and may become a potential drug.However,the number of such compounds extracted from plants is limited,and it is difficult to meet the amount to complete cell mechanism research.At the same time,the diversity of compounds with similar structures obtained from plants is limited,and it is difficult to satisfy the research on the structure-activity relationship between the molecular structure of the compound and the cytostatic activity.In this paper,the readily available dehydroepiandrosterone(DHEA)is used as the raw material for androsta-4(5),14(15)-diene-3,16-dione and12?-hydroxyandrosta-4(5),14(15)-diene-3,16-dione for semi-synthetic research.In this study,cyclic propyl methyl etherification,copper-mediated oxidation of the 12-position C-H bond,oxidative dehydrogenation of the 14,15-position,16-position ozonation,17-position samarium iodide reduction deoxygenation,and Oppenauer oxidation were used to treat the steroid framework A,C and D rings were modified,and two natural product molecules were synthesized through 9 and 12 steps respectively.At the same time,in order to meet the diversity of molecular structure for the study of the structure-activity relationship between the molecular structure of the compound and cell inhibition,the structure of the two natural molecules was modified in this paper,and a series of analogues were synthesized with high yield.The synthetic route designed in this study has the characteristics of universal method,simple operation,high yield and environmental friendliness.The structure of the obtained new compound was confirmed and characterized by nuclear magnetism,high-resolution mass spectrometry,specific rotation,and melting point determination.