Total Systhesis Of Natural Antibiotics:Benastatins,Anthrabenzoxocinones And Naphthacemycins

This dissertation is mainly focuses on total synthesis of aromatic polyketones natural products,which is divided into the following two parts:Part I: Total Synthesis of BenastatinsBenastatins belong to aromatic polyketides natural products.Studies have shown that these natural products show good biological activity against gram-positive bacteria including methicillin-resistant Staphylococcus aureus.For the synthesis of these natural products,a convergent synthesis strategy was adopted to achieve the synthesis of Benastatin B,F,G,and J.The key steps of the systhesis include: Photopromoted enolization Diels-Alder reaction to synthesize hydroanthracenol with geminal bismethylation quaternary carbon center.Cyclization reaction catalyzed by indium tribromide to build lactone rings;Photo-promoted radical cyclization reaction to construct the basic skeleton of Benastatin B,G and J;6? electrocyclization reaction to construct the basic skeleton of Benastatin A and F;Finally,Benastatin A,B(2.5%),F(6.3%),G(4.6%),J(4.1%)can be achieved in 10 steps starting from known compounds.This work will lay the foundation for their biological studies.In addition,the application of Photo-promoted enolization Diels-Alder reaction and photo-promoted radical cyclization will also lay the foundation for the synthesis of structurally related natural products.Part II: Total Synthesis of Anthrabenzoxocinones and NaphthacemycinsBy analyzing the structure of these two types of natural products,we hope to achieve the synthesis of these two types of natural products through a divergent route.Firstly,a nucleophile was prepared with the photo-promoted Diels-Alder reaction as the key step.Afterwards,the nucleophilic addition reaction was attempted to link the two fragments,but didn't get the target product.Subsequently,by adjusting the nucleophilic reagent into an electrophilic reagent,starting from the existing compound by reducing,introducing formyl and then oxidizing,the electrophilic reagent was prepared in 10 steps with an overall yield of 3.5%.Due to the uneconomical redox problem during the process,the subsequent introduction of the oxidation state in the unsaturated ketone and then using the photo-promoted enolization Diels-Alder reaction as the key step,electrophilic reagents was optimized in 11 steps with a yield of 3.5%.Finally,the preparation of advance intermediates of these two natural products was achieved by nucleophilic addition reaction,and we also prepared two analogues of natural products.This work will lay the foundation for the total synthesis of these natural products.