Synthetic Studies On Natural Products Hyperbeanol B And Stachybotrin C

In this thesis,the natural products Hyperbeanol B and Stachybotrin C were used as target molecules for synthetic studies with the dearomatization and aromatization reactions as key reactions,respectively.The subject of the application of dearomatization of phenolic compounds to construct quaternary carbon in total synthesis is reviewed,this thesis consists of the following three chapters:Chapter I Synthetic Study on Natural Product Hyperbeanol BMost of the polycyclic polyprenylated acylphloroglucinols compounds possess good anticancer activity,and in combination with their complex spirocyclic structure,the higher oxidation state have attracted much attention from synthetic chemists.The natural product Hyperbeanol B was isolated from Hypericum plantarum in 2011 and no synthesis has been reported so far,we designed oxidative dearomatization tandem Tsuji-Trost type reaction for the synthetic study of this compound.Starting from the natural chiral raw material（R）-Limonene（1-75）,the tri-substituted double bond was epoxided regionally selectively,followed by cleavage under the action of sodium periodate to obtain chain compounds containing both aldehyde and carbonyl groups,and then the aldehyde group was oxidized to carboxyl group by Pinnick oxidation to obtain 6-oxocarboxylic acid compounds.The Aldol reaction of carboxylic acid developed by Prof.Daniel Romo was used to obtain the tetrameric lactone compound and lactonization under the condition of 4-PPY as an auxiliary,the steric control of the two chiral centers at C8 and C9 was completed in one step under the induction of the isopropyl’s chirality,followed by the reduction of the lactone to diol compound 1-80 by the addition of aluminum lithium hydrogen.The tertiary hydroxyl group was protected and the primary hydroxyl group was oxidized to an aldehyde group to introduce an aromatic ring in a 1,2 addition reaction with a lithium benzene derivative.The isopropenyl group was oxidatively modified to give allyl carbonate analogues,the para-protective group was removed to give the ring close precursor compound 1-104.Using Pd（dba）₂ as catalyst and triphenyl phosphite as ligand,compound 1-104 underwent a critical oxidative dearomatization tandem Tsuji-Trost type reaction to successfully get the ring-closing compounds 1-99 and1-105,completing the synthesis of the tricyclic skeleton of the natural product Hyperbeanol B.The related studies are still in progress.Chapter II Synthetic Study on Natural Product Stachybotrin CStachybotrin C was isolated in 1997 from a culture of Stachybotrys parvispora strain F4708（Stachybotrys atra）,which contains two adjacent chiral centers in its structure,and the identification of its absolute conformation remained a challenge until 2018 when Professor Yoshikazu Kitano raised a single crystal by modifying the phenolic hydroxyl group with p-bromobenzyl bromide.Therefore,the asymmetric synthesis of Stachybotrin C is of particular importance.In our synthetic route,we take Sharpless asymmetric epoxidation to construct the chiral center,and the dihydropyran ring is constructed by opening epoxidation,in which the aromatic ring part is obtained by aromatization ofα,β-unsaturated ketones.Three methods of carbonyl insertion were tried for the isoindolin-1-one skeleton,and finally carbon monoxide was used as the carbon source,palladium metal as the catalyst,and copper acetate as the oxidizing agent to complete the carbonyl insertion reaction to construct the isoindolin-1-one fragment.Although the carbonyl insertion reaction has not been carried out in the real substrate,the conditions have been explored in the model reaction,and the related work is still in progress.Chapter III Application of Phenolic Compounds to the Construction of All Carbon Quaternary Carbons in Total Synthesis via Dearomatization StrategyDearomatization reactions are widely used in total synthesis and a series of remarkable results have been achieved in recent years.This chapter summarizes 53publications from 2000 to 2022 and aims to present some applications of phenolics in total synthesis through the construction of quaternary carbons by dearomatization.In this chapter,we divide this chapter into seven subsections according to reaction types:oxidative dearomatization-mediated[5+2]cycloaddition reactions,oxidative dearomatization-initiated Diels-Alder reactions,dearomatization cascade Heck-type reactions,dearomatization cascade Friedel-Crafts alkylation reactions,dearomatization initiated by rearrangement reactions,dearomatization cascade Tsuji-Trost type reactions,base-initiated dearomatization affinity substitution reactions.