Abstract: The process of phorbol preparation is complicated,in this study,the preparation process was optimized and the preparation cycle was shorten to 3 days.18 new compounds were designed and synthesized using phorbol,eicosapentaenoic acid,docosahexaenoic acid and arachidic acid.The compounds were characterized by ¹H NMR,¹³C NMR and HR-MS,and the toxicity of these compounds to hunan cells (MRC-5) was tested.There were 13 compounds with high cytotoxicity (IC₅₀< 38.12 μmol/L) and 5 compounds with low cytotoxicity (IC₅₀ > 100 μmol/L) in the cytotoxicity asssy.The phorbol-12-monoester and phorbol-13-monoester,which were esterified with long-chain saturated fatty acids had low cytotoxicity.The results of the test could provide guidance for phorbol structural modification.

Key words: phorbol, process optimization, structural modification, cytotoxicity