Total Synthesis Of Gukulenins Type Natural Products

Gukulenins are a type of natural product that belong to the class of marine terpenoids.These compounds are mainly derived from the sponge Phorbas gukulensis found in the sea off Korea.Gukulenins contain two highly functionalized α-tropolones that possess a cis 5-6 ring skeleton structure.The entire molecule has 10 to 11 chiral stereocenters,which includes 5 continuous chiral stereocenters and 2 all-carbon quaternary carbon chiral stereocenters.The unique and novel structure,as well as the diverse biological activities exhibited by gukulenins,have caught our attention.We aim to achieve the diverse synthesis of these natural products and explore their related biological activities further.The first part focuses on the construction of the core skeleton tropolone ring in Gukulens.Building upon previous research on the synthesis of the cycloheptatrienol ring,the study continues to investigate the cyclopropane ring-opening reaction to construct the core skeleton cycloheptatrienolone ring.The reduction method is utilized to selectively 1,2-reduce the ketone and reduce the oxidation state of the substrate.The successful synthesis of the cycloheptatrienolone ring is achieved through the elimination reaction and the ring-opening reaction of 6π electrocyclization.Experimental results further verify the feasibility of constructing the cycloheptatrienolone ring using the synthesis strategy of oxidative dearomatization and cyclopropanation ring expansion reaction.The second part of this thesis focuses on the synthesis of [5.6.7]tropolone ring monomer and [5.7] tropolone open chain monomer in Gukulens.Building upon the work of the first part,the synthesis of the cycloheptatrienolone ring with trans hydroxyl configuration is successfully achieved through the strategy of oxidative dearomatization and cyclopropane ring expansion reaction,as well as the reduction method.Methyl functional groups are introduced through selective bromination and Suzuki coupling reactions.The installation of the alkyne functional group is completed through the decarboxylation iodo and Sonogashira coupling reactions,and the [5.6.7] cycloheptatrienolone monomer in Gukulens natural products is successfully prepared.Starting from the [5.6.6] tricyclic skeleton,[5.6] open-chain monomers are synthesized through oxidative cleavage and decarboxylation.The method of oxidative dearomatization and cyclopropanation ring expansion reaction is also utilized to construct the core skeleton cycloheptatrienolone ring.The selective chlorination reaction and Suzuki coupling reaction are used to introduce the methyl functional group,and the preparation of the [5.7]cycloheptatrienol ketone ring-opening monomer is successfully completed.