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Integration of dynamic combinatorial chemistry and scale effect was designed to realize the efficient synthesis of bioactive compounds. Synthetic efficiency in the esterification reaction and combinatorial synthesis was significantly improved in smaller characteristic scale. Obvious increase in yield was observed when the reaction was conducted in the capillary with smaller diameters. More kinds of fatty acid esters were detected in the fixed bed flow reactor compared with the results in the flask. Based on the interaction of bioactive compounds and targets, the synthesis of compounds with high binding activity was intensified along with the dynamic shift of reaction equilibrium verified by gas chromatography. Uniform distribution of flow field would be beneficial to the mixing process, resulting in better mass transfer efficiency.