The Synthesis Of The New Kind Of Tanshinone Derivatives And The Research Of Biological Activity

This article contains two parts of the work,one was The synthesis of the new kind of tanshinone derivatives,and the another was the research of biological activity。The first part of the work includes the following three aspects:(1)The synthesis of the tanshinone derivatives.(2)Antitumor activity experiment of the tanshinone derivatives.(3)Antibacterial activity experiment of the tanshinone derivatives.(1)Through a large number of access to relevant reference we understanded that the compounds of tanshinones have a wide range of pharmacological activities,such as antitumor activity,antibacterial activity and so on.According to the principle of pharmacy splicing,the indole compounds with the same antitumor activity were combined with tanshinone,and the antitumor activity of the tanshinone derivatives was screened in vitro.It was hoped that the compounds with better activity molecular could be found.In addition tanshinone compounds have a certain antibacterial effect,by the antibacterial activity test in vitro of tanshinone derivatives,we hope to improve its antibacterial activity.Firstly,we designed the synthesis route of tanshinone Ⅰ and tanshinone Ⅱ A and indole,and the reaction was optimized.14 diindole fused tanshinone derivatives were synthesized.And then with pyrrole and tanshinone reaction,get 4 dipyrrole fused tanshinone derivatives.All compounds were tested for melting point,and the structure of the compounds was confirmed by1 H NMR、13C NMR、MS-ESI.(2)The MTT assay was used to study the anti-tumor activity of 18 compounds in vitro to tests the effects of K562(human chronic myelogenous leukemia),A 549(non-human small cell lung cancer),PC-3(human prostate cancer).The results showed that CZY-03,CZY-18 and CZYA-03 have relatively good activity for K562 and A549 tumor cells.Compounds CZY-03 have relatively good activity against A549 tumor cells.The antibacterial activity of the compounds was determined by the filter paper diffusion method(K-B method),and Escherichia coli and Staphylococcusaureus were selected to test the in vitro antibacterial activity of the above-mentioned tanshinone derivatives.The results showed that most of the tanshinone derivatives had a bacteriostatic effect on Gram-negative bacteria,and the antibacterial activity was higher than that of unmodified tanshinone at high concentrations,but the effect on Staphylococcus aureus Poor,most of the tanshinone derivatives are less active than unmodified tanshinones.The second part of the work:As the indole compounds have good antitumor activity,and indole structure appears in a large number of drug molecules or natural products,showing good biological activity,so we have 2-indolone as a research object,reserach the Methodology of synthesis of 3-alkoxy-2-indolone.We used 2-indolone as the starting material,after a multi-step reaction to get3-chloro-3-benzyl-2-indolone substrates,and then with a variety of common alcohol reaction,Alkoxy is introduced at the 3-position of 2-indolone.The synthesis method uses alcohol as the reaction substrate at the same time as its own solvent,sodium carbonate as a catalyst,at room temperature that is able to complete the reaction,the higher the yield,between 79%-93%,and ultimately we established a high efficiency,An environmentally friendly,inexpensive method of introducing an alkoxy group at the 3-position of 2-indolone.