New Drugs For Terminal Breast Cancer-Synthesis Process Development Of Fulvestrant

So far,the incidence of breast cancer occupies the first place in women cancer around the globe.Fulvestrant is a new type of Estrogen Receptors(ER)antagonist which is a drug for breast cancer.This drug can be used as a phase two treatment after ER therapy with no progress or menopause women with positive receptor.We will develop this drug,including the industrialized synthetic process and API quality standards,to satisfy domestic clinical need.The current Fulvestrant preparation is the laboratory synthetic process which is time consuming and expensive.It also requires favorable conditions which makes industrialization hard to achieve.Therefore,it is necessary to find an economic industrialization synthetic process.This paper mainly introduces an economic industrialization synthetic process that is applicable to Fulvestrant preparation.The Fulvestrant preparation introduced in this paper makes two breakthroughs in synthetic process:First,in the aspect of intermediate dehydronandrolon acetate preparation,we creatively use Silyl enol ethers and then use Ce4+ oxidative dehydrogention to get the objective product.This method promises a high yield in Fulvestrant preparation.Second,in long side chain and steroids parent 1,6-conjugate addition,the ee value is about 43%of the reported.Then,in our work,after adding appropriate chiral ligands the ee value is improved to 88%.This breakthrough improves the total yield of the Fulvestrant.In this paper,we use the simulation substrate for the technology research,Then get through the entire process.Second,we detailed study the two steps of the reaction route and substantial increased the yield.The first step is the preparation of the dehydrogenation nandrolone acetate,the second is to improve the ratio of the 7a isomer.After the detailed in-depth process optimization,the yield of the fulvestrant is 39.8%from the initial materials of nandrolone.