Total Synthesis Of Aspergillus A

As one of the biggest public health problems in the world,malignant tumor is serious hazard to human health and life,its morbidity and mortality rate is second only to cardiovascular diseases in all diseases.Anthraquinones are a kind of important secondary metabolites widely existing in nature,and have good antitumor activity on human lung cancer,liver cancer,lymphoma and so on.However,with the treatment time increasing,the toxic and side effects of natural anthraquinone and drug resistance of tumor cells gradually emerged,especially in the heart,which severely restricted the treatment of cancer patients.Therefore,it is very important to find a kind of antitumor drug with high efficiency and low toxicity.The secondary metabolites of marine organisms is more diverse,novel and unique due to the marine special living environment.In order to seek new drugs and solve the terrestrial resource crisis,people put forward the "to the ocean to drug" concept.Aspergiolide A(Asp A)is a novel anthraquinone compound and has good antitumor activity,it is found in marine mud from mangrove roots in the coastal areas of Fujian Province by the Gu Qianqun research group of Ocean University of China.Aspergiolide A is a novel compound with a novel naphtho [1,2,3-de]benzopyran-2,7-dione skeleton,which has broad spectrum cytotoxic activity and is strong against various human cancer cells.As an antitumor precursor of a novel anthraquinone structure,Aspergiolide A may exhibit different properties as do anthracycline anticancer drugs such as doxorubicin in terms of efficacy and cardiotoxicity.The content of Aspergiolide A in the original strain is extremely small,which greatly restricts its activity evaluation and structure-activity relationship research,so it is important to study the synthesis of such skeleton structure compounds.In this paper,four kinds of intermediate compounds(32,33,35,36)were synthesized by using 1,4-dihydroxyanthraquinone as model substrate in chemical inverse synthesis.We have carried out the optimization experiment of the conditionsof Knoevenagel ring-reduction reaction.Five kinds of naphtho [1,2,3-de] benzopyran-2,7-dione skeleton structural compounds were successfully synthesized by using two kinds of intermediate compounds.The total synthesis of Aspergiolide A has laid a good foundation for the subsequent development of Aspergiolide A and structural modification.All compounds were separated and identified by means of nuclear magnetic resonance(NMR)and liquid chromatography-mass spectrometry(LC-MS).