Asymmetric Diels-Alder Reaction Based On The Total Synthesis Of Genepolide

Terpenes are a whole family of natural products widely existing in nature.terpenes characterized with novel structures and various bioactivities are constantly a key concern in the biomedicine and chemistry fields.More and more organic chemists turn to the study on the total synthesis of these terpenoids with complex structures in recent years,which has been pushed by the discovery and development of asymmetric Diels-Alder reaction.Sesterterpenes,a special type of terpenoids,although less quantity,have important commercial value in virtue of excellent biological and pharmacological activities.The studies on extraction and isolation and total synthesis of sesterterpenes are not slim.Genepolide as a kind of sesterterpene with novel structure and high-activity was isolated in 2008 by the research group of chemist Appendino from the mountain wormwood,it involves new sesquiterpeneγ-lactone structure and could be a formal Diels-Alder adduct of sesquiterpene costunolide and myrcene.There are no reports on the synthesis of this molecule to date.So we try to deliberate the total synthesis of genepolide.Previous studies revealed the infeasible total synthesis of genepolide and suggested this substance was not an isolation artifact but a genuine natural product.Fortunately,we got the final adduct of Diels-Alder reaction on intermediate as trying to screen conditions constantly.We have already started work on two aspects on this research simultaneously.On the one hand,we have obtained an optimal synthetic process on intermediate by the way of retrosynthetic analysis,so we got the key Diels-Alder adduct in seven steps started from santonin.On the other hand,we carried out the methodological study on asymmetric Diels-Alder reaction based on the viability between intermediate and diene.Such as Structural changes and modifications,screening different kind of dienes and Condition optimization of Diels-Alder,to gain an optimum condition,during this process,we got some adducts successfully,which could be used as a corroboration of our conclusion.In the end,we started the total synthesis of genepolide from the intermediate and accomplished the synthesis of the precursor of cope rearrangement in nine steps beginning with the intermediate.In the final step,we could not acquire the desired results with continually trying in follow-up work.However,the impracticable D-A reaction have been successfully realized,which makes the total synthesis of genepolide clear.This study could be a referential significance to other total synthesis of natural products.