Objective: To synthesis 4'-N

N-Bis-substituted (aminomethyl) benzoate ether derivatives of scutellarein with improved anti-oxidative activity

and investigation of their protection against nerve cells oxidative damage. Method: Scutellarein 2-bromoethyl ether (4) was synthesized in the presence of 1

8-diazabicyclo[5.4.0]undec-7-ene (DBU) with scutellarein and 2-bromoethanol as starting materials. N-substituted (aminomethyl) benzoic acids (5a-c) were converted to benzoic chloride (6a-c) by using oxalyl chloride

then the latter coupled with 4 in the presence of 4 MS to obtained compounds (7a-f)

then diphenyl ketal protecting group of the above compounds was removed by using acetic acid chloride/methanol system to obtain target compounds(8a-f)

prodrugs were tested for their cytotoxicity and antioxidant activity in PC12 cells by MTT and LDH leakage rate assay. Result: The structure of synthesized compounds 8a-f was confirmed by the methods of 1H-NMR

ESI-MS. The results indicated that compound 8e and 8f have more potent anti-oxidative activity than positive control Vitamin E. Conclusion: The synthetic method we used has preferable practicality and can be used in synthesizing scutellarein 4'-N

N-bissubstituted (aminomethyl) benzoate ether derivatives

bioactivity evaluation results suggested that the kind of prodrugs are worthy of further investigation to discover new anti-oxidative agents.