Design,Synthesis And Bioactivity Studies Of Gastrodin And Gastrodigenin Derivatives

Gastrodin(p-hydroxymethylphenyl-β-D-glucopyranoside)is the major and bioactive component extracted from an ancient Chinese herb Tianma(Gastrodia elata Blume).Gas has many pharmacological effects,including sedation and hypnosis,intelligence enhancement,anticonvulsant properties,brain nourishment,antioxidant activity,senility postponement,immunologic defense enhancement and improvement in the accommodation of the heart and blood vessels.Gastrodigenin(p-Hydroxybenzyl alcohol),is an aglycone of gastrodin and one of the components in Tianma.Pharmacodynamic study has shown the gastrodin in blood mainly as Gastrodigenin.Gastrodigenin has pharmacological effects similar to Gastrodin.In this paper,we use the principles of combination to design gastrodin and gastrodigenin derivatives.In the synthesis of gastrodigenin derivatives,we use p-hydroxybenzaldehyde as lead compound,and combined it with nicotinic acid、cinnamic acid and 3,4,5-tri(acetyloxy)-benzoic acid through ester linkage or combined with(3,5,6-trimethylpyrazin-2-yl)methanol through ether linkage,Subsequent reduction with NaBH4 resulted in benzyl alcohol.The compound 4-[(3,5,6-trimethylpyrazin-2-yl)methoxy]Benzenemethanol combined with nicotinic acid.3,4,5-tri(acetyloxy)-benzoic acid、succinic anhydride and 4-hydroxybutanoic acid through ester linkage or combined with ethyl 4-hydroxybenzoate、4-hydroxybenzaldehyde through ether linkage.The compound 3-pyridinecarboxylic acid 4-(hydroxymethyl)phenyl ester combined with nicotinic acid、succinic anhydride through ester linkage.A total of 18 gastrodigenin derivatives were synthesized including 14 new compounds.In the synthesis of gastrodin derivatives,we use acetagastrodinum as lead compound,and combined it with cinnamic acid、Acetylsalicylic Acid、3,4,5-tri(acetyloxy)-benzoic acid、nicotinic acid、succinic anhydride and 4-hydroxybutanoic acid through ester linkage or combined with vanillic aldehyde、4-hydroxybenzaldehyde and ethyl 4-hydroxybenzoate through ether linkage,and 9 gastrodin derivatives were synthesized.Most of gastrodin and gastrodigenin derivatives were verified by IR spectrum,1HNMR spectrum,13CNMR spectrum,MS spectrum,and the synthesized compounds were screened for their inhibitory effect on angiotensin-converting enzyme(ACE)in vitro.The positive control drug:captopril,and most of the compounds have a better ACE inhibitory activity.The preliminary biological results obtained from our experiments have demonstrated that compound A5 presents an excellent ACE inhibitory activity(inhibited 85%of ACE),and closely to the captopril(inhibited 95%of ACE),which provided the foundation for studying on the structure-activity relationship of gastrodin and gastrodigenin derivatives and further pharmacological activity research.