The natural benzodihydrofuran neolignans licarin A (1) was synthesized from isoeugenol through biomimetic oxidative coupling. Then licarin A (1) was transformed into another benzodihydrofuran compound 2-(3'-methoxy-4'-hydroxy)- phenyl-3-methyl-5-formylvinyl-7-methoxy-2,3-benzodihydrofuran (2) through 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) oxidative reaction. Based on Mannich reaction of 1 or 2 with viarious secondary amines and formaldehyde in acidic alcohol system under microwave-assistanced, eleven new benzodihydrofuran neolignan Mannich base derivatives 3～13 were synthesized. All the synthetic compounds were tested for antiproliferation activity against human cervical carcinoma Hela cells by the standard CCK-8 method. The results showed that most of the target compounds exhibited moderate to potent antiproliferation activity against Heala cells. Among them, compound 2 (IC₅₀ 0.438 μmol/L) and compound 9 (IC₅₀ 8.358 μmol/L) displayed the strongest antiproliferation activity against Hela cells.

Key words: benzodihydrofuran, licarin A, Mannich base derivatives, synthesis, biological activity