Toadflax Synthesis And Activity Of Acid Derivatives

Linarinic acid is a novel chiral tricyclic quinazolin alkaloid. Its recent progress, the optimization of the reported total synthesis technology, the synthesis of linarinic acid derivatives and its bioactivities were discussed in this paper.According to the reported total synthesis of linarinic acid, some improvements were achieved in the synthesis technology of linarinic acid. The yield was increased from 35% to 50% by replacing flash column chromatography with recrystallization in the work-up of the final step of the total synthesis route. Furthermore, some study was carried out on the reagents in the third step of the total synthesis.Based on the optimized total synthetic route of linarinic acid, 25 derivatives of linarinic acid were designed and synthesized. Among these target compounds, there is a nitrated derivative of linarinic acid, which was not easy to identify where the nitro group was introduced. Therefore ~1H NMR and H,H-NOESY were employed in the structure identification to find the 7-nitrolinarinic acid as the only product of the nitration. Then 7-aminolinarinic acid was obtained by reduction of 7-nitrolinarinic acid. Other target compounds were synthesized by using substituted o-nitrobenzaldehyde as the starting material. Structures of final products and important intermediates were all characterized by NMR and MS spectra. Specific rotations of final products were measured.Preliminary pharmacological evalutions showed that linarinic acid and all the 5 tested compounds and linarinic acid dose-dependently reduced the content of MDA in liver of elder rat in vitro. LA-6 is the most effective compound. When inhibition rate of MDA is 50%, the concentration of LA-6 is 0.957nM. The pharmacological tests of other derivatives are under progress.