Study On The Synthesis Process And Derivatives Of Anti-diabetic Lead Compound Fla-CN

Objective Tiliroside was the main anti-diabetic constituent isolated from Potentilla chinensis Ser.Fla-CN,a tiliroside derivative with strong anti-diabetic activity,has been synthesized.It can regulate glycogen metabolism and significantly improve the glucose consumption in the insulin resistant HepG2 cells through activating a signaling molecule named AMPK in liver cells.It can also promote the translocation of GLUT4 in skeletal muscle cells(L6 and C2C12 cells),as a result increasing glucose metabolism in skeletal muscle cells.Therefore,Fla-CN is a kind of anti-diabetic lead compound with novel structure.To establish a suitable synthesis process for a high yield,we explored the preferred reaction conditions including reaction temperature,substrate concentration,reactants proportion and the catalyst by single-factor experiments.In the previous study,the cyano group of Fla-CN was found to play a key role for the anti-diabetic activity.In this work,we synthesised the derivatives which were the potential metabolite of Fla-CN refferring to the common metabolite of cyano group.It was researched that whether there was a metabolic activation phenomenon of lead compound Fla-CN in vivo.Further structure-activity relationship of Fla-CN was also studied.Methods 1.Study of the synthesis process of Fla-CN:The target compound Fla-CN was prepared from 4-cyano benzaldehyde and kaempferol via Claisen-Schimidt condensation,a-bromination of the α,β-unsaturated ketone,and etherification reaction.To establish a suitable synthesis process for a high yield,we explored the preferred reaction conditions including reaction temperature,substrate concentration,reactants proportion and the catalyst by single-factor experiments.2.Synthesis of Fla-CN derivatives:With the above synthesis process for reference.Target derivatives were synthesized from 4-formylbenzoic acid and kaempferol via amidation,esterification,Claisen-Schimidt condensation,a-bromination of theα,β-unsaturated ketone,etherification reaction and hydrolysis reaction.The synthetic compounds were identified by organic spectrum methods.Results 1.The synthesis process of Fla-CN in this paper goes as follows.To prepare intermediate 1,4-cyanobenzaldehyde is refluxed for 24 hours in acetone with morpholinium trifluoroacetate as catalyst.Intermediate 2 is prepared when the temperature is 30 centigrade,the proportion of intermediate 1 and PHT is 1:1,the dropping concentration of PHT is 0.06 mol/L,and the reaction time is 24 hours.Fla-CN is synthesized when the temperature is 80 centigrade,the proportion of intermediate 2 and kaempferol is 1:1.2,the concentration of intermediate 2 in reaction solution is 0.08 mol/L,and the reaction time is 8 hours.The total yield is 50.5%.2.Thirty nine compounds were synthesized,including twenty eight intermediates and eleven target derivatives.All compounds were identified by organic spectrum methods.All derivatives are the new compounds which haven’t been reported before.Conclusion The synthesis process of anti-diabetic lead compound Fla-CN was built on the basis of previous synthesis work in the light of its three reaction steps.Single factor experiments were adopted to explore the optimum reaction conditions in this research.Total yield of Fla-CN is significantly increased.According to its possible metabolites,we designed and synthesized eleven derivatives which haven ’t been reported before.