Synthesis And Biological Activity Studies Of Nauclefine And Steroidal Derivatives

Nauclea alkaloids and steroids are very important natural product.They show excellent biological activities and specific structural skeleton,all of these facts have drawn great attention from chemists.In this dissertation,we successfully synthesised nauclea alkaloids angustine,subditine as well as their derivatives based on the previous by reported strategy.We also preliminarily explored their structure-activity relationship(SAR)through detected compounds inhibitory effect on Hela cell activity.In addition,we completely modified steroids containing the structure of ketene by PEDA reaction.Firstly,we have got angustine in steps of 10 and a yield of 13% through hydroamination-lactamization cascade reaction.Simultaneously,we synthesized subditine in 5 steps and a yield of 7%,which utilized traditional electric cyclization reaction,also defined structure via X-ray.We modified this family structure of C-10?19 and 20,and studied the SAR between substituents of these sites and anti-cervical cancer Hela cells,which provided foundation for further research on medicinal chemistry.Secondly,we modified the A ring of steroids with ketene structure through PEDA reaction,which reacted under light and lewis acid.We obtained some anthraquinone skeleton of steroids,all of these were examed for cytotoxicity of liver cancer?prostate cancer and leukemia.Among of them,we found compound 3-65 have strong cytotoxic activity against leukemia cell line Reh and CCRF-CEM.