Synthesis, anti-virus and anti-tumour activities of dibenzylbutyrolactone lignans and their analogues

An efficient synthesis of dibenzylbutyrolactone lignans and their analogues has been developed. Based on a Stobbe condensation of piperonal or veratraldehyde with diethylsuccinate and alkylation with 3,4-methylenedioxybenzyl bromide to give the skeleton of the lignan. The (+/-)-diacid was resolved with quinine and the functional groups were transformed to obtain three benzylbutyrolactone lignans and seven analogues. Four natural lignans were prepared by this method, and five lignans were synthesised for the first time. The synthesised compounds were evaluated for anti-HIV, anti-HSV, and anti-tumour activities. Results showed that the dibenzylbutyrolactone lignans and their analogues were inactive against HIV Tat transactivation and HSV-1 in vitro, but some compounds displayed significant activity against MDA-MB-435 human breast cancer cell.