The Total Synthesis Of Natural Product Curcumenol

This thesis aimed at the study on the total synthesis of guaiane-type natural product sesquiterpenoid Curcumenol.The research progress of natural products in guaiane sesquiterpenoid was reviewed.These compounds with a five-seven membered ring skeleton have highly biological activities.Up to now,many natural products including Englerin A,Orientalol F,have been successfully synthesized by organic chemists,and the first total synthesis of Curcumenol was studied in this thesis.The [5,7]oxatricyclic ketone 137 was obtained through 12 steps using readily available 3-butyn-1-ol as starting material.Among them,Evans asymmetric methylation reaction led to the formation of chiral acid 165 with high stereoselectivity,which provided the chiral core of this natural product.Furthermore,the preparation of cyclic precursor compound 136 was furnished.After the construction of [5,7]oxatricycle ketone,this thesis focused on the introduction of ethoxy carbonyl group at the α-position of ketone.LDA/acetone/ZnCl2,LDA/ethyl cyanoformate,and NaH/dimethyl carbonate(DMC)were tested,respectively.Methoxy carbonyl group was successfully introduced by using DMC in the presence of NaH,which provided an opportunity for the construction of isopropylidene group.The rhodium-catalyzed intramolecular carbonyl ylide cyclization cycloaddition tandem reaction(CCCC reaction)is described as the key step in this synthetic strategy.