Synthesis And Structure Modification Of Several Natural Steroidal Molecules

Steroid is a kind of natural products,with many bioactivities.Therefore,synthesis and structure modification of natural steroids are meaningful.In this thesis,synthesis and modification of several steroidal natural molecules were focused,including two parts:1.Synthesis of Solanidine: Solanidine is a steroidal alkaloid,with unique chemical structure and variety of bioactivities.Tian et.al had completed a synthesis of solanidine from diosgenin,featuring a Schmidt rearrangement and suffering from severe epimerization of C-25 stereochemistry.To address the epimerization issue,the synthetic route was re-designed,tin order to prepare solanidine and 22-epi-solanidine divergently.Starting from diosgenin acetate,Solanidine was synthesized in nine steps with an overall yield of 24% and 22-epi-solanidine in nine steps with an overall yield of 17%.Noteworthy transformations include: a ring-switching process to open ring E,an epimerization of C-25,a selective reduction of lactone via a reduction-relay process,a Schmidt rearrangement/N-alkylation/reduction process,and a double N-alkylation process.2.Synthesis of Steroid-topiramate Conjugates: Topiramate is a new clinical used anti-epilespy drug,and the total glycosides of Cynanchum otophyllum were used to treat refractory epilepsy with Phenytoin clinically.The principle of the glycosides is owe to the C21 stereoidal glycosides.Based on the structures of caudatin,the predominant aglycone of the glycosides,and torpiramate,the similar skeleton with the sugar linkage of the glycosides,the conjugates of Steroid-topiramate were designed,and twelve new compounds were synthesis,6 of them are conjugates and the others are derivatives of steroid 3-sulfonate.