Study On The Design, Synthesis And Activity

(-)-Linarinic acid,is a new compound isolated from the ethanol extract of the whole herb of L.vulgaris Mill.by Hua et al.The programe of PASS was used to predict the activity of Linarinic acid.The result showed that the Linarinic acid had a significant activity of stimulate cardiovascular.The design and synthesis of the novel Linarinic acid and Pyrrolo[2,1-c][1,4] benzodiazepine-3,11-dione derivatives and its anti-brain ischemia physiological activity were reported in this dissertation.Linarinic acid is a novel chiral tricyclic quinazolin alkaloid.According to the reported total synthesis of linarinic acid,some improvements were achieved in the synthesis technology of linarinic acid.Based on the optimized total synthetic route of linarinic acid,the derivatives which were donating-electron group,amide,carbonyl at 9 site,and benzylidene at 3 site with linarinic acid were synthesized.In the progress of synthesis of Linarinic acid and its derivatives,we got another kind of compound named Pyrrolo[2,1-c][1,4]benzodiazepines.Some literatures reported this kind of compound had anti-ischemic activitiy.12 derivatives of linarinic acid and 11 derivatives of Pyrrolo[2,1-c][1,4]benzodiazepine-3, 11-dione were designed and synthesized by using optimized total synthetic route of linarinic acid,the target compounds were synthesized by using substituted o-nitrobenzaldehyde as the starting material.Structures of final products were all characterized by ~1H-NMR and MS spectra.Specific rotations of final products were measured.Preliminary pharmacological evalutions of 5 tested compounds showed that 4 derivatives of linarinic acid dose-dependently reduced the content of MDA in liver of elder rat in vitro and three compounds showed stronger inhibition effects than lead compound Linarinic acid;LA-10 can be effective to extend survival time of the rats,and also be effective to reduced the content of MDA in liver and cerebra of rats.So they have good activity of anti-brain ischemia activity. The pharmacological tests of other derivatives are under progress.The mentioned above may make theoretical and practical bases for future work on the project searching for more potential leading compound.