Total Synthesis and Anti-Tobacco Mosaic Virus Activity of the Furofuran Lignan (±)-Phrymarolin II and Its Analogues

Phrymarolin II, a furofuran lignan
isolated from Phryma
leptostachya L., features a 3,7-dioxabicyclo[3.3.0]­octane
skeleton. Herein, we report an alternative total synthesis of (±)-phrymarolin
II (2), which was performed in 9 steps from commercially
available sesamol. The key steps of the synthesis included a zinc-mediated
Barbier-type allylation and a copper-catalyzed anomeric O-arylation. Our total synthesis allowed the synthesis of analogues
of (±)-phrymarolin II. Most derivatives displayed good to excellent in vivo activity against tobacco mosaic virus (TMV). (±)-Phrymarolin
II (2) and compounds (±)-31d and (±)-31g exhibited similar or higher activity than commercial ningnanmycin, which
indicated that phrymarolin lignans are a promising new class of plant
virus inhibitors.