The Synthesis Research Of Natural Products Madindolines

Natural products research has always been an important part in the field of new drug research and development, due to the nature resource of natural products is very limited, organic synthesis play a decisive role in natural products research. The study found that natural products Madindolines have a very good activity in inhibiting tumor cell growth, alleviating cancer cachexia, are expected to be effective anticancer drug. Unfortunately, the original source no longer produces these antibiotics. Therefore, the chemical synthesis becomes the only source of Madindolines.Firstly, we concern the discovery, separation, biological activity and skeleton structure characteristic of Madindoline A and B. Reported synthetic strategies of the two important skeleton structure unit of Madindolines,3a-hydroxyfuroindoline ring structure unit and cyclopentene-1,3-dione structure unit have been demonstrated as a simple review. And detailed analysis of reports on the total synthesis of Madindolines were reviewed, focusing on the research of cyclopentene-1,3-dione structure unit.On the basis of the application of the Darzens/ring expansion process of cyclobutenedione developed previously by our group, a new strategy to the multi-substituted cyclopentene unit of Madindoline A and Madindoline B has been reported. In the light of the strategy, the synthesis of racemic Omura's intermediate was finished in 4 steps and with 34% overall yield, which furnished a new formal synthetic route to Madindolines A and B. We also did a series of work on substrate extension to Darzens/ring expansion process, which enriched the cyclopentene-1,3-dione compound libraries, and laid a solid foundation to the activity research for future. On this basis,2-chiral quaternary carbon cyclopentene-1,3-dione structure unit has been tried to build on a range of hard work.