Studies On Total Synthesis Of Dasyscyphin B And Optimization Of Synthetic Route Of Anti-Cancer Lead Compound NHTD

This thesis consists of three chapters.Firstly,the applications of natural（+）or（-）-carvone as a chiral starting material towards the total syntheses of natural products in the past five years（2017-2021）are reviewed.Then,the total syntheses of dasyscyphin B and habiterpenol were studied.Finally,the synthetic route of anti-cancer lead compound NHTD was optimized.Chapter 1 The applications of carvone as a chiral pool in total syntheses of natural products（2017-2021）Carvone is a cheap and readily available natural chiral source,which is easily transformed into various useful building blocks.It is often used as a chiral starting material for the asymmetric syntheses of terpenoids and terpenoid alkaloids.In this chapter,we mainly summarized the applications of carvone as a chiral pool in total syntheses of natural products in recent five years（2017-2021）.Chapter 2 Total synthesis of merosesquiterpenoid dasyscyphin B and meroditerpenoid habiterpenolIn this chapter,we firstly introduced the isolation,structural characteristics,bioactivity of dasyscyphins A-G and their relevant synthetic research works.Then we chose dasyscyphin B（the one with the best bioactivity）as our target,then designed and attempted three synthetic routes to construct its core structure.The first synthetic route featured an intramolecular Nazarov cyclization reaction to construct the targeted 6/6/5/6tetracyclic skeleton or 6/5/6 tricyclic skeleton.Unfortunately,the conversion rate of this key step could not be improved or the coupling block could not be prepared smoothly,this route had to be abandoned.So we turned and explored other more efficient synthetic routes.The second route featured an intramolecular Heck reaction as the key transformation to construct the targeted 6/6/5/6 tetracyclic skeleton.However,under the explored common conditions of Heck reaction,only γ,δ-desaturated products were obtained.Our third route was to construct a tetracyclic skeleton through twice Robinson cyclization reactions.And now we have successfully constructed the requisite 6/5/6 ring system.At the same time,a more complex natural analogue habiterpenol was also chosen as our synthetic target.Firstly,its isolation,structural characteristics,physiological activities and previous synthetic research work were briefly introduced.Then we designed and tried a convergent strategy to construct the requisite pentacyclic core via a tandem Diels-Alder reaction/Nazarov cyclization reaction.Unfortunately until now we have not found the suitable conditions for the reaction.After that,we planned to develop a general synthetic route which featured a Catellani reaction as the key step to complete the collective syntheses of dasyscyphins and habiterpenol.And this route is attempted in our laboratory now.Chapter 3 Optimization of the synthetic route of anti-cancer lead compound NHTDIn this chapter we firstly introduced the discovery of anticancer lead compound NHTD and its reported synthetic method.Then the synthetic route was optimized to provide sufficient amounts of NHTD for further research.（This part is a cooperation project between Yao’s group and us.）...