Study On Synthesis Of New Lignans And Its Biological Activity

Lignans with significant biological activity are a class of natural metabolites, which widely exist in plant roots, stems, leaves and fruits. In this paper, We studyed from builting the skeleton of lignan compounds--phenylpropanoid to its coupling reaction. Using different types of catalytic reaction, lignan compounds got high yields ,detected by biological activity which is a new class of biologically active lignans. The major findings are as follows:1. At first, a cheap compound of the 2,4,5 - trimethoxy benzaldehyde was choosed as an intermediate, evaluated the optimal experimental conditions and synthesised representativeα-asarone. In order to get lignan compounds with a series of different configurations, the reseachof substrates is necessary. Benzaldehyde derivatives that were choosed as substrates by Witting or Grignard reagent, were synthesised as different configurations of lignan skeleton unit.2. In Mn （II） / Co （II） / O₂ Redox System, benzene generation of alkene derivatives composed new lignan compounds under 24h with acetic acid. It just so happened that under H+/PhP（O）HOR catalyst System whitout solvent the action goes well. Optimization of experimental conditions, compound had higher yields than the former, especially,α-asarone got 95% yields, the yields of 4-methoxy-styrene were twice as much as that of Mn （II） / Co （II） / O₂ Redox System. Studying from the result of compouds yields, it’s found that electron withdrawing group make reaction happen difficultyly, however, electron donating group is beneficial to reaction. Steric hindrancs is the key factor to reaction, because aryl-alkene whit one methoxy group make reaction happen easier than two methoxy groups. And it’s more economical and environmental.3. In vitro cell inhibition for Bel-7402 cells （human hepatoma cell）、MCF-7 cells （human breast carcinoma）、A549 cells （human lung cancer cell） and Hela cells （human cervical cancer cell）of prodrugs were measured by MTT method. It showed that lignans compounds on human hepatoma cell line are most effective, the IC50 values of 2b compound is18.9μg/ml. It was found that the effect of compounds on cancer cells depends on time. In contrast to LO₂ cells （normal human liver cells） , it found that compounds in the inhibition of cancer cells while normal cells are also killed in a certain extent. Analyze anti-cance mechanism of compounds: Hoechst33342-PI double staining were used to observe morphology, and flow cytometry （FCM） were used to detect DNA content changes of cell cycle.4. The structures have a close relationship with the activity, all of the compounds the same as Taxol make the number of the phase G2/M of Bel-7402 increase, which indicate that all of the compounds have the inhibition of DNA replication. The compounds of 2a, 2b, and 2f have good biological activity and induce cancer cells to apoptosis, which indicate that more electron donating substituent groups of benzene can enhance the biological activity of compounds; 2b makes the G0/G1 phase of cancer cells reduce higher than 2a, indicating that the more side chains of compound the more activity; 2f makes the G0/G1 phase of cancer cells reduce higher than 2e by 4.97%, indicating the position of substituents on the benzene ring is important to activity; two adjacent methoxys of benzene increase electron density of the benzene ring, and make compound activity increase.