Structural Modification Of Fla-CN Unsaturated Ketone Fragment

Objective Potentilla flavonoids is the main active ingredient for the anti-diabetic activity of the Chinese traditional medicine Potentilla.Previous endeavors in our group has synthesized Fla-CN,a derivative of Potentilla flavonoid with strong anti-diabetic activity.By activating AMPK signaling molecules in liver cells(Hep G2 cells),this compound significantly improved glucose consumption and reversed insulin resistance.Moreover,it can promote GLUT4 translocation in skeletal muscle cells(L6 and C2C12 cells)and increase glucose metabolism in skeletal muscle cells.Therefore,Fla-CN is a leading compound with a novel structure as well as anti-diabetic activity.In this paper,we designed two types of Fla-CN derivatives under the guidance of the traditional pharmaceutical chemistry theory.The unsaturated ketone fragment in Fla-CN was replaced with either conventional carbon chain or a nitrogen-containing heterocyclic ring replace,to obtain compounds with better anti-diabetic activity.Methods Fla-CN and kaempferol was used as raw materials.The target derivative was prepared using reduction reaction,click chemistry,Sonogashira reactions and 1,3-dipolar cycloaddition reaction.Its chemical structure was characterized using organic spectroscopic.Results54 different compounds,including 7 intermediate and 47 target derivatives were synthsized.Chemical structures of all compounds were characterized by nuclear magnetic resonance spectroscopy.Conclusions With the unsaturated ketone fragment of Fla-CN replaced by conventional carbon chain or a nitrogen-containing heterocyclic ring,we designed and synthesized two types of derivatives of antidiabetic lead compound Fla-CN.All target derivatives are novel compounds without previous literature report.