Syntheses of C(18) dibenzocyclooctadiene lignan derivatives as anti-HBsAg and anti-HBeAg agents

(+)-Gomisin K(3) (1) and kadsurarin (2) were isolated from Schizandra arisanensis and Kadsura matsudai, respectively, and a series of C(18) dibenzocyclooctadiene lignan analogues (5-20) derived from 1 and 2 were synthesized. Esterified derivatives of 1 and 2 were evaluated for inhibitory activity against human type B hepatitis with surface antigen (HBsAg) and e antigen (HBeAg). Most of the analogues (5-8, 10, 12-13) derived from 1 exhibited higher anti-HBsAg effects and lower toxicity, and 6, 7, 8 and 12 also showed higher anti-HBeAg activity. Among these active C(18) dibenzocyclooctadiene lignan analogues, the lignan with a but-3-enoyl group (6) exhibited the most active inhibition.