An Investigation Into The Synthesis Of C-7 Ingraftation Decorated Steroidal Aromatase Inhibitor

Steroidal aromatase inhibitor can inhibit the aromatase activity, interdict the reaction, and inhibit the estrogen formation, so that it can cure the breast cancer. For its speciality and durative, aromatase inhibitor as a drug for the breast cancer has gained wide attention. It can be used to clinic. Steroidal aromatase inhibitor has the similar structure with the androstenedione(AD) , which can be used to synthesize aromatase. AD is very cheap and has the rich resource. In this dissertation designs steroidal aromatase inhibitor with the position of C-7 ingraftation decorated, studies synthesis of compound or its intermediate and corroborates the structure of compound through IR NMR MS.Firstly, thesis investigates oxidation of AD and gets the mixture with the AD as the material and DDQ as oxidant. The reaction is influenced greatly by acid. With benzene as the solvent, Mainly gets the 3-3 without the acid catalyst, purity and yield can get up to 97.5%, 76.1%。thesis gets the 3-3 with the acid containing water. with dioxane as solvent, its purity and yield are 95.9%, 50.3%. with the weak acid, the benzene as the solvent , gets the 3-3 purity and yield of 97.1%, 88.7%。with the strong acid without water, the benzene as the solvent, gets the 3-2 purity and yield of 96.5%, 68.3%. Rising up the temperature and more catalyst or long time of reaction can make the 3-3 more stable but make the trend that the 3-2 would transfer into 3-3. In the reaction, it needs large quantity of strong acid catalyst, so has to get the final single product with the columniation chromatogram separation method. With this method, the yield was very low and there were many outgrowths, and the later treatment is very complicated. Thesis gets the intermediate 3-2 with the AD as the material and chloranil as oxidant. The outgrowth rate is very low. The most proper condition is : with chloranll as oxidant, 1.1:1 for the eq ratio of oxidant vs AD, 3h for the reflux. Under the condition we got the purity and yield of 98.6%, 72.6% with recrystal method.Secondly, thesis gets the intermediate 3-2 as the material and then mended it with the even ingraftation decorated. Inducted the ethyl and butyl through the Grignard reaction, and gets the yield of 37.2%,30.9% respectively. And inducted the thioethyl, thiophenyl, sulfoxidephenyl, thiohydroxypropylthio, thioethylamino, through Michael reaction, and gets the yield of 40.1%,80.4%,28.5%,92.1%,87.9% respectively.Finally, thesis gets 3-16 through substituent reaction with 3-10 as the material, total yield is 66.3%.