Synthesis and structure–activity relationship of 3-O-acylated (–)-epigallocatechins as 5α-reductase inhibitors

Abstract A series of 3- O -acylated (–)-epigallocatechins were synthesized and their inhibition of steroid 5α-reductase was studied. They were prepared from the reaction of EGCG with tert -butyldimethylsilyl chloride followed by reductive cleavage of the ester bond. The resultant (–)-epigallocatechins penta- O - tert -butyldimethylsilyl ether was esterified with different fatty acids then desilylated to provide the corresponding products. The activity of 3- O -acylated (–)-epigallocatechins increased with the increasing carbon numbers of the fatty acid moiety, reaching maximum for 16 carbon atoms (compound 4h ) with an IC 50 of 0.53 μM, which was ∼12-fold more potent than EGCG (IC 50  = 6.29 μM). Introduction of monounsaturated fatty acid provided the most potent compound 6 (IC 50  = 0.48 μM), which showed moderate anti-tumor activity in vivo .