A Novel Synthetic Route For Estra-4,9-diene-3,17-dione And 19-nor-4-androstenedione

Steroid hormone drugs are the second largest class of drugs after antibiotics,and they are clinically indispensable.Estra-4,9-diene-3,17-dione is also known as Estradienedione.It is an important intermediate for the synthesis of drugs such as mifepristone and dienogest.19-nor-4-androstenedione,also known as methyl ketone(Norandrostenedione),It is an important precursor for the synthesis of norethisterone and pHenylpropionate.At present,the demand for these drugs at home and abroad has increased year by year,and has a very broad market prospect.In this paper,the synthesis methods of Estra-4,9-diene-3,17-dione and19-nor-methyl-androstenedione were summarized and designed.Choose a relatively simple raw material and a synthetic route that is better to operate.Mainly based on theδ-Lactone.((6aR,9aR)-6a-methyloctahydrocyclopenta[f]chromene-3,7(2H,8H)-dione)as the starting material.Synthesizing the above two drugs by a multi-step chemical reaction,The route has been optimized and discussed in order to be suitable for industrial mass production.Synthesis of Estradiol-4,9-diene-3,17-dione: starting from the δ-Lactone,Estradiol-4,9-diene-3,17-dione was synthesized by Grignard reaction,oxidation,ring closure,deprotection and reclosed,with a total yield of 58.4%.Synthesis of 19-nor-1,4-androstenedione: starting from the δ-Lactone,19-nor-4-androstenedione was synthesized by Grignard reaction,oxidation,ring closure,reduction,deprotection,and reclosed route.The total yield was 59.6%.The process has been optimized and improved during the synthesis process.The corresponding steps have been analyzed and studied to suit industrial production.At the same time,the structure and purity of the intermediate product and the target product were determined by nuclear magnetic resonance and high performance liquid chromatograpHy.