Chem. Pharm. Bull. 54(2) 226—229 (2006)

have attracted considerable attention recently for their antioxidative and antimutagenic activities (Chart 1). Lignans are generally accessible only through multistep syntheses and/or direct isolation from the living plant. Lyoniresinol (1) was isolated via extraction of the Lyonia ovalifolia var. elliptica plant. Compound 1 was also obtained by enzymatic hydrolysis of lyoniresinol glucoside with cellulase. In this paper, we report the synthesis of 1 with the combined utilization of synthetic chemistry and biotechnological methods, specifically using plant cell cultures as an “enzyme source.” The biosynthetic pathway generally postulated for the podophyllotoxins (lignans in general), as shown in Chart 2, involves enzyme-catalyzed oxidative coupling of dibenzylbutanolide to the cyclic lignan in the later steps of the pathway (from 2 to 3). Such ring-closure reactions (phenol oxidative coupling) are considered to be achieved through peroxidase (POD) enzymes present in the plant. Kutney et al. reported horseradish peroxidase (HRP)–H2O2 catalyzed ringclosure reactions with phenolic systems: enzyme-catalyzed ring-closure reaction of dibenzylbutanolides suitable for biotransformation to lignans as potential intermediates. However, the addition of H2O2 to the reaction mixture resulted in red-brown darkening of the solvent which decreased the chemical yield. Recently, we have found that Camellia sinensis cell culture is an efficient source of POD as “reagents” in organic synthesis and that a huge amount of H2O2 is produced in plant cell cultures with the addition of foreign substrates. Thus we planned to construct the skeleton of 1 using C. sinensis cell culture (as an enzyme source)-catalyzed ring-closure reaction of dibenzylbutanolide (11) as the target synthetic intermediate to cyclic product 12 via a hypothetical quinone methide intermediate (A), as shown in Chart 3.