Skeleton Construction Of Tetrahydroxanthones And Synthetic Studies Towards The Total Synthesis Of Ascherxanthone A&Dicerandrol C

This thesis focuses on synthetic studies of tetrahydroxanthone natural products,which includes construction of the tetrahydroxanthone core and studies toward the total synthesis of dimeric tetrahydroxanthones.Part 1:Construction of tetrahydroxanthone core.We have developed a new methodology using photo-induced C-O bond formation to construct the skeleton of tetrahydroxanthones.A fracture of C-Cl bond was achieved by activating the C-Cl bond using ultraviolet light and followed by adjacent oxygen atoms involved cyclization.This reaction proceeds under mild conditions which tolerates various substrates and functional groups.Espectially for the dimeric substrates,it forms two rings at the same time.This methodology opens a new door for the total synthesis of tetrahydroxanthone natural products.Part 2:Studies toward the total synthesis of dimeric tetrahydroxanthones.Ascherxanthone A belongs to tetrahydroxanthone homodimer which includes methyl group in the tetrasubstituted carbon center,and it shows biological activity on anti-malarial and anti-tumor.This synthetic strategy features(1)constructed the tetrasubstituted carbon center by an asymmetric allylic C-H oxidation,(2)accomplished the formation of C ring to complete the synthesis of monomeric ascherxanthone A by an intramolecular aldol reaction,(3)tried to achieve dimerization by applying the strategy of intramolecular oxidative coupling,but it failed,and the dimeric tetrahydroxanthone ascherxanthone A was obtained by one-pot Suzuki-Miyaura coupling.The absolute configuration of ascherxanthone A was first established by comparision of spectra and X-Ray.The synthesis discolsed a new approach to preparing structurally related natural dimeric tetrahydroxanthenones and carried a foreshadowing of medicinal studies.Dicerandrol C belongs to tetrahydroxanthone homodimer which includes hydroxymethyl group in the tetrasubstituted carbon center,and it shows the inhibition of Staphylococcus aureus and cytotoxicity.As for the synthesis of its monomer,we have developed:(1)RCM reaction to form the C ring,(2)employed benzaldehyde dimethyl acetal to selectively protecting the alcohols,but it didn't give the desired product,and finally,selective protection of the second alcohol was realized by adjustment of solvents,(3)applied SNAr reaction to connected it with an aromatic ring,(4)tried to use the nucleophilic addition of carbonyl a position to the cyano group,but it didn't work,and completed the construction of ABC ring using intramolecular aldol reaction at last.This part of work laid the foundation for the total synthesis of related natural dimeric tetrahydroxanthenones.