Synthesis And Application Of Penicillium Ketal Compound Core Skeleton

Benzospiro ketal natural products are widely distributed in nature,with novel and complex structures,many types and good activities.In recent years,it has attracted great attention and in-depth research from organic chemists and pharmacologists.Among many natural products,the peniciketals family of penicillium ketals has unique and novel benzospiro ketal and benzo bridged ketal skeletons,which are complex in structure and full of challenges in the synthesis work.Peniciketals have good inhibitory activity on leukemia cells and lung cancer cells,and have weak toxicity to normal human cells,making them a class of potential cell proliferation inhibitors or anti-tumor agents.So far,the synthesis of peniciketals family of penicillium ketals has been reported,but there are still many synthetic difficulties to be overcome,and the development of simple and efficient synthetic strategies is still the common goal of scientific researchers.In this thesis,an acid-catalyzed spirocyclization strategy is proposed to simultaneously construct the benzospiro ketal and benzo bridged ketal skeletons in one step to realize the efficient synthesis of peniciketals.In the synthesis of peniciketal B,it was found that acid-catalyzed spirocyclization can construct the benzo[6,6]-spiro ketal skeleton in the next step under mild conditions.From this opportunity,try to use the above ring-building method to explore another natural product Synthetic studies of citreoviranol.The main content of this thesis is divided into three parts:Part 1: Briefly describe the classification of benzospiro ketal natural products,and briefly introduce the source distribution,isolation and identification,structural characteristics and biological activities of some representative natural products,and briefly introduce the construction of benzospiro ketals Skeleton construction method.The second part: briefly introduces the source distribution,isolation and identification and biological activity of the peniciketals family of penicillium ketals,and summarizes the total synthesis of peniciketals of penicillium ketals.The retrosynthetic analysis and synthetic route of peniciketal B were drawn up,and the synthesis of key intermediates was explored through the investigation of key reactions.The skeleton of benzo[6,6]-spiro ketal has been successfully constructed.The third part: briefly introduces the source distribution,isolation and identification and biological activity of citreoviranol and isophthalic acid lactone family(RALs)with similar structures,and briefly describes their reported synthesis work.The retrosynthetic analysis of citreoviranol was proposed,the synthetic route was drawn up,and the key intermediate 3-26 was synthesized.