The Total Synthesis Of Halenaquinone-Type And Pleurotin-Type Natural Products

This thesis focuses on the total synthesis of halenaquinone-type and pleurotin-type natural products,which were based on the development of PEDA reaction.Part one:The methodological studies of PEDA/oxidation(dehydration)/aromatization reactions and the total synthesis of xestoquinone,adociaquinones A and B.Halenaquinone-type natural products belong to a class of naphthoquinone or naphthol compounds,that exhibited potent bioactivities.Regarding to the total synthesis of this family of natural products,we firstly studied the PEDA/oxidation(dehydration)/aromatization reactions using sterically hindered dienophiles.The study indicated that the Lewis acid Ti(Oi-Pr)4 played a pivotal role in this PEDA reaction,which could activate the sterically hindered dienophiles and control the selectivity of PEDA reaction.Through studying the substrate scope of PEDA/oxidation/aromatization sequence including aromatic aldehydes and sterically hindered cyclohexenones,17 cyclohexanonefused naphthols including the core skeletons of garveatin C have been synthesized efficiently.Besides,the PEDA/dehydration/aromatization sequence of aromatic aldehydes and sterically hindered cyclopentenones were also studied and 18 cyclopentanone-fused naphthalenes including the core skeletons of exiguaquinol were achieved.On the basis of these methodological study,we then studied the total synthesis of xestoquinone and adociaquinones A?B.The related strategy in this total synthesis are 1)Using desymmetric intramolecular Michael reaction to construct the bridgehead quarternary carbon;2)Using PEDA/aromatization reactions to construct the naphthalene skeleton;3)Using acid-promoted furan ring formation and late-stage cyclization to complete the synthesis of natural products' skeleton.Based on these strategy,the asymmetric total synthesis of(+)-xestoquinone,(-)-xestoquinone and(+)-adociaquinones A?B were successfully achieved in 6-7 steps with respectively 17.9%,16.6%and 15.0%yields.This work not only achieved the asymmetric total synthesis of(+)xestoquinone,(-)-xestoquinone and(+)-adociaquinones A?B but also developed the Ti(Oi-Pr)4-promoted PEDA reaction.Part two:The total synthesis studies of natural products pleurotin,dihydropleurotinic acid and 4-hydroxypleurogrisein.We first successfully synthesized the A-B-C core skeleton of pleurotin which bearing two stereocenters at C-17 and C-18 utilizing the asymmetric PEDA reaction.Then the A-B-C-D core skeleton of pleurotin was successfully assembled with the help of Wacker oxidation and aldol condensation.We also affirmed the practicability of retrosynthetic analysis through the exploration of stereoselective hydrogenation,olefination and hydroboration-oxidation reactions.Besides,the total synthesis of 4-hydroxypleurogrisein was also studied.The A-B-C-D core skeleton of 4-hydroxypleurogrisein was successfully assembled through the three steps sequence of dihydroxylation,Wacker oxidation and aldol condensation.Afterward,the isomer of 4-hydroxypleurogrisein was synthesized using stereoselective hydrogenation,Mukaiyama oxidation,olefination and dihydroxylation as crucial reactions.In conclusion,this work laid the foundation for the total synthesis of pleurotin-type natural products.