Synthetic Studies Toward 2,5-Dihydroxy-Homoverrucos-(3)-ene

In 2020,Houwen Lin and his team at the Center of Marine Medicine Research,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,isolated a new type of Homoverrucosane tricyclic diterpene natural product 2,5-dihydroxyhomoverrucos-(3)-ene and its related natural products from sponge Halichondria sp for the first time.2,5-Dihydroxy-homoverrucos-(3)-ene is a diterpenoid with a 7-6-5tricyclic skeleton and six continuous chiral centers,so its chemical synthesis is challenging.In this thesis,we take oxidopyrylium [5+2] cycloaddition reaction as the key step to attempt the total synthesis of 2,5-dihydroxy-homoverrucos-(3)-ene,which mainly includes the following two chapters:The first chapter systematically introduces oxidopyrylium [5+2] cycloaddition reaction,including the classification of oxidopyrylium [5+2] cycloaddition reaction and its application in total synthesis.The second chapter introduces the classification,biogenic pathway and synthesis of 7-6-5 tricarbocyclic diterpenes and related compounds,the separation of 2,5-dihydroxy-homoverrucos-(3)-ene and its related compounds and the research progress of the total synthesis of 2,5-dihydroxy-homoverrucos-(3)-ene in our research group.2,5-Dihydroxy-homoverrucos-(3)-ene and its related compounds are Homoverrusane tricyclic diterpenes with 7-6-5 tricyclic skeleton system and 6 continuous chiral centers,which are challenging to synthesize.Starting from(R)-limonene,the advanced intermediate 2-109 with 7-6-5 skeleton was obtained by intramolecular asymmetric Michael addition reaction,Achmatowicz oxidative rearrangement reaction and oxidopyrylium [5+2] cycloaddition reaction,and then the oxygen bridge bond in the seven-membered ring was successfully opened to form compound 2-139,paving the way for the accomplishment of the total synthesis of 2,5-dihydroxyhomoverrucos-(3)-ene and its related natural products.