Study On The Asymmetric Total Synthesis Of Natural Product 4-epicurcumenol

Guaiane-type sesquiterpenes have attracted many attentions of organic chemists and medicinal scientists due to their diverse bioactivity such as antibacterial,antitumor,anti-inflammatory,antioxidant（NO inhibition）,anti parasite and acute myeloid leukemia treatment.In this paper,the discovery,structural type and biological activity of guaiacane sesquiterpenoids has been reviewed.The[5,7]oxygen bridge ring structure of 4-Epicurcumenol was successfully constructed with3-butyyne-1-alcohol as the starting material.The total yield of this synthesis is 0.48%.Among them,many crucial reactions have been used to build the ring core framework of 4-Epicurcumenol,including the Evans asymmetric methylation at C-4 position of 2-8 with high stereoselectivity;the CCCC reaction of diazoketone to building[5,7]oxygen bridge catalyzed by Rh（II）;Aldol reaction of 2-16a by the addition of acetone under the synergistic effect of LiHMDS and ZnCl₂ at-30°C;And finally the dehydration of 2-17a with catalytic amount of p-TsOH in C-7 position to introduce isopropenyl group.All the carbon skeletons have been constructed after 18 steps with the total yield of0.48%,which made preparation for the total synthesis of 4-Epicurcumenol.