Synthesis And Characterization Of Deoxycholic Acid Derivatives,and The Studies Of The Anticancer Activity

Deoxycholic acid,which is a kind of triterpenoid organic compounds,is widely distributed in the nature,and shows a variety of biological activities,such as the treatment of liver disease and gallstones,antibacterial activity,antimalarial activity,anti-angiogenesis activity,especially anticancer activity.Most anticancer drugs have different degrees of liver damage.Chemical treatment of cancer is still lack of an antitumor drug which can protect normal liver cells.Deoxycholic acid is exactly expected to fill this gap.Scientific workers have also screened a lot of bile acid derivatives which have remarkable anticancer activity.But at present,they pay less attention to deoxycholic acid.Therefore,we introduce amino acids and heterocyclic compounds into the structure of deoxycholic acid,in order to get the deoxycholic acid derivatives which have better anticancer activity,higher bioavailability and less side effects.This thesis is mainly divided into three parts:The first part:Briefly introducing the research progress of deoxycholic acid,cholic acid,their derivatives,their pharmacological actions,and applications for molecular recognition and polymer chemistry materials.Also prospecting their developments.The second part:Design,synthesis and characterization of deoxycholic acid derivatives.Forty new derivatives were synthesized,details are as followed:1.Esterification the C-24 carboxyl of deoxycholic acid,then combination its C-3hydroxyl with carboxyl of the seven amino acids whose amino groups have been protected.After removing the protecting groups,thirteen amino acid derivatives are synthesized（DA-2（a^g）、DA-3（a^g））.2.After protecting the C-3 hydroxyl of methyl deoxycholate,reducing its ester group into alcohol,then coupling it with protected amino acid.After removing the protecting groups,sixteen amino acid derivatives are synthesized（DA-4⁵、DA-6（a^g）、DA-7（a^g））.3.Introducing the connecting fragment of butanedioic acid into the C-3 hydroxyl of methyl deoxycholate,then coupling it with N-Boc-piperazine and morpholine.Afterremoving the protecting groups,four heterocyclic derivatives are synthesized（DA-8、9（a^b）、10）.4.Transforming the C-3 hydroxyl of methyl deoxycholate into methylsulfonyl oxyethyl.After that,transforming it into azido group,two derivatives are synthesized（DA-11¹2）.5.After protecting the C-3 hydroxyl of methyl deoxycholate,either reducing its ester group into carboxyl,or oxidizing C-12 hydroxyl into carbonyl.Then reducing the ester group of the carbonyl product into carboxyl,on the other hand,removing the protecting groups of C-3 hydroxyl,four derivatives are synthesized（DA-13¹6）.Forty new compounds were characterized by IR,¹H NMR and ¹³C NMR.The third part:The study of anticancer activity of deoxycholic acid derivatives.The results showed that DA-3a、DA-3g、DA-12 had anticancer activities to MCF-7 and Hela,DA-7a、DA-8、DA-16 had anticancer activity to Hela.