The Synthesis And Structure Activity Relationships Research Of Antitumor Steroidal Saponins

For further structure-activity relationships(SAR) research of steroidal saponins, especially furostan and cholestan saponins,we used natural products icogenin and OSW-1 as the lead compounds,designed and synthesized a series of derivatives of natural products.All of the work in this paper can be divided into three parts:1.The design and synthesis of icogenin derivativesIn order to study the role and contribution of the trisaccharide residue in icogenin,we employed the simplified disaccharide[α-L-Rhap-(1-2)-β-D-Glcp]and[α-L-Rhap-(1-2 )-α-D-Glcp]replacing the trisaccharide moiety of icogenin,synthesized a pair of epimeric icogenin derivatives.Through the cytotoxic activities research of these two derivatives,and activity comparison to icogenin and three typical steroidal saponins,we made progress in the research of cytotoxicity mechanism of these compounds.2.The synthesis of cholestan saponin derivatives and furostan saponin derivatives Using natural product diosgenin as raw material,three cholestan derivatives were synthesized via a concise and efficient route.When another synthetic route was tried, three furostan derivatives were gotten.All of the chemical structure of the six compounds in this part were confirmed by ¹H-NMR,¹³C-NMR and LC-HRMS.3.The research for synthesis route of 15-hydroxy cholestan aglyconeWhen diosgenin was used to synthesize the target 15-hydroxy cholestan aglycone,5, 6-double bond in diosgenin caused great trouble.To avoid the affection of 5,6-double bond,we try to use tigogenin,which is lack of 5,6-double bond,to replace disogenin following the same synthetic route.