Studies On Synthesis And Biological Activities Of Aminosteroidal Derivatives

Aminosteroids is an important type of steroidal compounds, which elicit diverse biological activities. Introduction of nitrogen-containing group to the steroidal skeleton by the chemical synthesis is one of the most important way to develop steroidal medicine. The thesis was comprised of five chapters, which mainly basing on the design, synthesis, characterization and biological evaluation of aminosteroidal derivatives as potential anticancer agents.Chapter 1 was the introduction of steroidal compounds,which including structural features, classification and aminosteroidal drugs used clinically. Then, the recent progress in the structure modification and activity which focused on the A,B,C and D ring respectively was reviewed. The main idea of the thesis was also concluded in the end.In chapter 2, a series of 16E-arylidene-3-heterocyclic-5a-androstane derivatives were synthesized efficiently starting from Epiandrosterone via condensation, oxidation, reductive amination, reduction and esterification procedures in high yields. All of these new compounds synthesized were unreported before, and their structures were confirmed by IR,’H-NMR,13C-NMR, MS, Single crystal X-ray diffraction and elemental analysis.In chapter 3, a series of 16β-azolyl-3β-amino-5a-androstane derivatives were synthesized efficiently starting from Epiandrosterone via 16-bromide, oxidation, introduction of azoles, reductive amination, reduction and esterification procedures in high yields. All of these new compounds synthesized were unreported before, and their structures were confirmed by IR,1H-NMR,13C-NMR, MS, Single crystal X-ray diffraction and elemental analysis.In chapter 4, the anticancer activities of 16E-arylidene-3-heterocyclic-5a-androstane derivatives and 16β-azolyl-3β-amino-5α-androstane derivatives were determined by MTT assay. We summarized the structure-activity relationship of the two types of aminosteroidal derivatives on the basis of activity data.In chapter 5, the main conclusions and novelties of the thesis were summarized.