Studies On Synthesis Of Sequiterpenes And Antihypertension Medicine

This thesis aims at the studies on the total synthesis of bicyclic sesquiterpenes and the novel and efficient synthetic strategy of Valsartan,a kind of medicine for hypertension.This thesis consists of the following five parts:Part one:The asymmetric total synthesis of eudesmane sesquiterpenesA novel approach for the enantioselective construction of the naturally occurring C-1 oxygenated 10-epi-eudesmane skeleton starting from(+)-dihydrocarvone was accomplished.This approach relies on a substrate controlled hydromethylation to introduce the C-1 oxygenated group,a regioselective aldol reaction and a alkaline Robinson cyclization to assemble the decalin skeleton.The total synthesis of 1-oxygenated-10-epi-eudesmane,which is the key intermediate for the synthesis of complex eudesmanolides,was achieved.This strategy was further used in the first asymmetric total synthesis of the enantiomers of natural 1β-hydroxy-eudesma-5,11-diene and 1β,11-dihydroxy-5-eudesmene.And the stereochemistry of the C-4 methyl group in natural 1β,11-dihydroxy-5-eudesmene was revised fromαtoβ.Part two:The first total synthesis of ligudentatin ALigudentatin A,a new phenolic norsesquiterpenes,was first synthesized starting from(+)-perillaldehyde through five steps,successively,in an overall yield of 20.8%. The key steps were the Diels-Alder reaction and aromatization of enone to phenol.Part three:An Efficient Enantiocontrolled Synthesis of Dihydromayurone and (-)-ThujopseneDihydromayurone which could be converted to(-)-thujopsene by the published method was efficient enantiocontrolled synthesized starting from (+)-dihydrocarvone through 9 steps in an overall yield of 19.3%,respectively, including Simmons-Smith reaction as the key step.Part four:A simple and efficient synthesis of the valsartanValsartan,one of the most important agents used in antihypertensive therapy today,was synthesized starting from L-valin methyl ester hydrochloride through 4 steps in an overall yield of 60%.The key step involves the palladium-catalyzed Suzuki coupling.This method overcomes many of the drawbacks associated with the previously reported syntheses and is more suitable for industrial production.Part five:ReviewIn this part,some published approches for synthesis of thujopsenes and some published methods for construction of C-1 oxygenated eudesmane type bicyclic sesquiterpenes were reviewed.