Objective  To evaluate the synthesis of caffeic acid derivatives and their targeting on brain.   Methods  Methyl and ethyl esters of caffeic acid were synthesized by direct reaction of caffeic acid to methanol and ethanol with sulfate acid used as a catalyst. 3

4-diacetyl caffeic acid was synthesized by acetyla-ting caffeic acid with phosphate acid used as a catalyst. Their partition coefficient (P) in 1-octanol-phosphate buffer system (pH 7.4) was detected. An in vitro blood brain barrier (BBB) model was established by co-culturing brain capillary endothelial cells (BMVEC) and astrocytes (AC) for the evaluation of their targeting on brain.   Results  The partition coefficients (P) of the three derivatives were much higher th

an that of caffeic acid

and their lipophilicity was stronger than that of caffeic acid. The potency of methyl ester of caffeic acid and 3

4-diacetyl-caffeic acid across the in vitro BBB was better than that of caffeic acid.   Conclusion  The structure of three synthesized caffeic acid derivatives can be conformed by MS

1

HNMR

IR

and UV spectra. Methyl ester of caffeic acid and 3

4-diacetyl-caffeic acid can cross the BBB and can thus be used as brain targets.