Total Synthesis Of Bicyclic Sesquiterpenes And The Novel And Efficient Synthetic Strategy Of Valsartan

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. It consists of the following four parts:Part â… : Studies on the total synthesis of bicyclic sesquiterpenes. A novel approach for the enantioselective construction of the naturally occurring C-1 oxygenated 10-epi-eudesmane skeleton starting from (-)-carvone was accomplished. The key steps in the synthesis include substrate controlled Mukaiyama Aldol reaction, selective Grignard reaction, alkaline Robinson cyclization, Reduction Rearrangement reaction, selective Epoxidation and so on.Part â…¡: Studies on the synthetic strategy of Valsartan.The novel and efficient synthesis of Valsartan was achieved starting from 4-bromotoluene, 4-bromobenzyl bromide or 4-bromoaldehyde by three different methods. The target compound was cut off from the middle of the two benzene ring of Biphenyl Tetrazole and the key step was accomplished through Suzuki Coupling reaction. It's worth to mention that our goal was to minimize the use of hazardous and expensive metals and increase the overall efficiency of the synthesis. Furthermore, the saponification of the methyl ester in Valsartan was realized in a convenient and economical manner, which is more suitable for industrial production.Part â…¢: Studies on the dehydro-rearrangement reaction of the 1,6-dioxo-8α-methyl-1, 2,3,4,6,7,8,8α-eight hydrogen-naphthalene and its analogues with DDQ. In this part, the dehydro-rearrangement reaction of eudesma-4,11-dien-3,9-diones, 9-hydroxy (or 9-actoxy)-eudesma-4,11-dien-3-ones and their analogues with DDQ were deeply studied. And the rearrangement reaction of 9- actoxy-2,5- dienones under K₂CO₃/MeOH was covered The mechanism of these two rearrangements was also discussed in detail.Part IV: ReviewIn this part, some published methods for construction of C-l oxygenated eudesmane type bicyclic sesquiterpenes were reviewed.