Study On The Synthesis And Biologocal Ativity Of Aza-steols And Aza-spiro Compounds

Steroids are widely found in nature and contained in humans,plants,animals,and minerals,which exhibit good biological activities.Aza-steroids refer to a compound formed by introducing a nitrogen atom or a nitrogen-containing functional group into a steroid skeleton or its branched chain.In recent years,many studies have found that some new aza-steroids showed good biological activities and some of them even have developed into clinical drugs.Cholesterol is an important active substance,and its derivatives also have good biological activity.According to the application of bioisosterism in lead optimization,the introduction of nitrogen atoms or nitrogen-containing functional groups on the cholesterol core or side chains can make the compound have a wider range of biological activities.Based on the previous research of our group,in this dissertation,two kinds of C-6 aza-sterols were designed and synthesized.Then we carried out the condensation with different acyl chlorides to synthesis 46 new aza-sterols which were characteried by NMR and X-ray diffraction.The biological activities of these compounds will be evaluated and the SAR will be analyzed to provide new ideas and references for the further study.Spiro compounds as an important intermediate in organic synthesis with stable structure,anomeric effect,spiro-conjugation and other special properties play an important role in many fields such as biomedicine and emerging materials.We intend to develop a method for the construction of multi-spiro compounds using high-valent iodine reagent as oxidate.We synthesized key intermediates 2-26 and 2-35 starting from the p-hydroxyaniline and p-hydroxypropionic acid.After a series of spirocyclization works,the desired spiro[5,6] and spiro[5,5] ring compounds were not obtained.Instead,the oxazole spiro compounds 2-51 were detected and laid the certain foundation for the future research in our laboratory.