Study On Synthesis Of 17β-estradiol And 17α-ethinylestradiol 3-ether Compounds And Their Pharmacological Activity

The research of estrogens has several decades of history, and it has a certain degree of biological potency, but its application is limited often due to the high activity of estrogen and the serious side effects. Estrogens has the better prevention and treatment to the radiation injury. As an anti-radiation drug, the study of estrogens has nearly 60 years history at home and abroad, but often due to its strong activity of estrogen and side-effects on the stomach intestine and the liver, as well as suspecting its potential carcinogenic activity because of the side effect of thickening uterine basement membrane, its application is limited in the relevant areas. The anti-radiation effect of estrogens has a close relationship with the chemical structure of estrogens. So in the course of the study on the anti-radiation drug, how to find a homologue of estrogen, which has stronger anti-radiation effect and less side effects, is still an important part of the research on the anti-radiation drug of estrogens.In order to find an anti-radiation drug of estrogens which has high anti-radiation effect and low harmful side-effects, we decide to choice estradiol and ethinylestradiol as leading compounds and transform the chemical structure of the both compounds through method of synthesis. Four compounds have been designed and synthesized and they are estradiol-3-allyl ether,ethinylestradiol-3-allyl ether,estradiol-3-isopentenyl ether and ethinylestradiol-3-isopentenyl ether. The steps of synthesis is short, the yield is high, the conditions of reaction are not very harsh, and the raw materials for reaction are also easy to get, so it is suitable for industrial production and valuable to continue to further research on the technology of industrial production. The chemical structures of the four new estrogen derivatives were confirmed by MS, IR, ¹H-NMR and ¹³C-NMR.The pharmacological experiments of anti-radiation biological potency and improving the function of blood potency of the four new compounds have been done. The experimental results showed that estradiol-3-allyl ether and estradiol-3-isopentenyl ether have significant effect of improving the number of white blood cells which is decreased by ray, and so it is very valuable to further study.