Estrone And Estrogen Derivatives

Along with social progress, economic development, changes in the concept of human life, as well as the acceleration of China's aging population, Estrogen drugs will increasingly demand. How to solve the problem of lack of raw materials, develop novel and more effective estrogen drugs, improve the economy of drug R & D and production and so on, are tough challenges to overcome these problems for people. Based on the reaseach results of our research group, my dissertation is concerned on investigating 1,2-dehydrogenation of 19-hydroxyandrost-4-ene-3,17-dione 1-04 with DDQ as oxidant and utilizing the dehydrogenation of 1-04 steroids with subsequent A-ring aromatization via retro-aldol-type fragmentation reaction provided a flexible and efficient protocol for the synthesis of estrogens.In order to investgating the 1,2-dehydrogenation of 1-04, firstly we use various common types of hydroxyl protecting groups to protect compound 1-04, and then examined their 1,2-dehydrogenation with DDQ as oxidant and dioxane as solvent under reflux condition. The study found that if it does not protect or use of ether hydroxy protecting group can't occur. If the protecting group of the type is ester , the reaction react quickly.To demonstrate the utility of the protocol, pharmaceutically attractive estrogens were synthesized from easily available 19-hydroxy-4-ene-3-keto steroids, such as estrone, 6,7-dehydroestrone, 6,7-epoxy estrone and 3-Etherified estrone. Besides we studied the synthesis of 3-amino estrone and H8-BINOL steroid derivant. These new synthetic methods have not been reported, synthetic routes simple, high yield, product quality, to avoid the application of a wide range of toxic reagents.Throughout the paper, it's a better way for the synthesis of estrogen drugs.