Studies On The Synthesis Of Naphthoquinone Diterpenoid Pleurotin With Antitumor Activity

Pleurotin is a naphthoquinone diterpenoid compound with antibacterial and antitumor activity,which was isolated by Robbins’ research group from basidiomycetes in 1947.Its structure was confirmed by degradation and single crystal diffraction.Pleurotin showed inhibitory activity against Gram-positive bacteria,and the National Cancer Institute reported Pleurotin had a good inhibitory effect on Trx-1activity.This thesis takes Pleurotin as the research object,including the following two chapters:Chapter 1: The isolation,structure identification,biological activity and biosynthetic hypothesis of Pleurotin are systematically introduced.And the synthesis of Pleurotin was introduced in detail.In 1988,David J.Hart’s research group completed the first total synthesis of Pleurotin with the yield of 1.8% starting from the racemic advanced intermediate in 18 steps.In 1991,George A.Kraus’ s research group synthesized the tetracyclic advanced intermediate of Pleurotin by tandem Photoenolization/Diels-Alder reaction.In 2022,Erik J.Sorensen’s research group completed the formal total synthesis of Pleurotin in 13 steps.Chapter 2: This part mainly introduces the synthesis of Pleurotin with DielsAlder reaction as the key reaction by our research group.In the first-generation synthesis of Pleurotin,we obtained the tetracyclic advanced intermediate of Pleurotin by Diels-Alder reaction.In the second-generation synthesis of Pleurotin,we obtained a stable core skeleton of Pleurotin through Dorz reaction,Hydroxy-directed DielsAlder reaction,and Pd/C catalyzed hydrogenation.Among them,Hydroxy-directed Diels-Alder reaction can construct the tetracyclic skeleton of Pleurotin and quaternary carbon in one step.Pd/C catalyzed hydrogenation reaction can achieve the efficient reduction of dissubstituted double bond,tetrasubstituted double bond and ketocarbonyl group in one step.So far,we have obtained the core tetryclic skeleton of Pleurotin and developed the Hydroxy-directed Diels-Alder reaction.And the reaction can rapidly construct the core skeleton of Pleurotin and its derivatives.