The Biomimetic Synthesis Of Hassanane And Salyunnanin A

In this paper,the biologically active C₂₃ terpenoid natural products hassanane and salyunnanin A were structurally verified and revised by synthesis.In addition,an exploration study on the construction of chiral quaternary carbon by asymmetric allyl alkylation has been carried out.This artical includes two chapters.Chapter 1 the Biomimetic Synthesis of Hassanane and Salyunnanin AC₂₃ terpenoid natural products hassanane and salyunnanin A have similar structure,which were isolated from the acetone extract of white sage and the root of yunnan sage,respectively.Luis and his coauthors speculated that hassanane contained unique cyclooctyltrienedione structure by the NMR data analysis.According to the structure,Luis speculated the biosynthetic pathway of hassanane,and believed that apianane,a natural product of C₂₃ terpenoid,was the biosynthetic precursor of hassanane.In 2008,Zhao qinshi found the spectra data of hassanane and przewalskin A were similar.It was speculated that hassanane may possess a tropone structure.In order to test their hypothesis without samples,Zhao calculated by the ¹³C nuclear magnetic chemical shift and UV-visible absorption spectrum of quantum mechanics and compared with experimental data.The results showed hassanane with tropone structure was more reasonable than cyclooctyltrienedione structure.Total synthesis is a direct and powerful method to determine the precise chemical structure of natural products.Therefore,we propose to confirm the structure of hassanane by synthesis.Carnosol was prepared from commercially available carnosic acid by oxidation and esterification under acidic condition.In the condition of sodium methoxide and methanol,carnosol was converted into 7-methoxyrosmanol through the multi-step transformation of lactone ring opening,isomerization,oxidation and double Michael addition of methanol.The o-benzoquinone was obtained by mono-protection of phenolic hydroxyl in 7-methoxyrosmanol and subsequent oxidation.Then the o-benzoquinone reacted with bismuth ylide prepared in-situ to synthesize hassanane.Comparing the hydrogen and carbon spectra of the synthetic and isolated compounds,it was found that the spectra data were consistent,which confirmed the structure of hassanane and the hypothesis of Zhao qinshi.The natural product salyunnanin A was isolated and identified by Xu gang's group in 2014.The relative stereochemistry of salyunnanin A was speculated that6,7-H was in cis structure,based on the weak correlation of ROESY spectrum.We speculated and analyzed the biosynthetic pathways of salyunnanin A and hassanane in the process of biomimetic synthesis of hassanane.We speculated that the synthetic precursor of salyunnanin A was rosmanol,which the compound 6,7-H was in trans structure.Therefore,6,7-H of salyunnanin A may also be in trans structure.In order to verify the speculation,we carried out the total synthesis of salyunnanin A with carnosol.In the condition of sodium bicarbonate,carnosol was converted into natural product rosmanol,then followed 2 hydroxy protection and remanent phenolic hydroxyl oxidation to get corresponding o-quinone.The o-benzoquinone reacted with Bi-ylide prepared in-situ to expand the ring to obtain the corresponding tropone compound,followed the TBAF removal protection to furnish the synthesis of salyunnanin A.By comparing the spectra data of the synthetic and isolated compounds,we found that the spectra data were consistent.In order to further verify the structure of salyunnanin A,we obtained the C7 epimer by redox of synthetic compound,with the single crystal structure of the salyunnanin A reported by Xu gang.The results showed that the spectral data of the compound of 6,7-H in trans was consistent with the natural product salyunnanin A,and the structure of salyunnanin A was revised accordingly.Chapter 2 Studies on the Allylic Alkylation to Construct Chiral Quaternary CarbonThe construction of chiral quaternary carbon is not only one of the research hotspots of organic chemistry but also one of the challenges.This chapter mainly introduces asymmetric allyl alkylation for constructing chiral quaternary carbon of natural products.