Synthesis and chiral HPLC analysis of the dibenzyltetrahydrofuran lignans, larreatricins, 8'-epi-larreatricins, 3,3'-didemethoxyverrucosins and meso-3,3'-didemethoxynectandrin B in the creosote bush (Larrea tridentata): evidence for regiospecific control of coupling.

The creosote bush (Larrea tridentata) lignans are linked via 8-8' bonds, with the simplest apparently being E-p-anol derived. Of the latter, four of the six theoretically possible diastereoisomers were isolated, namely (-)-larreatricin, (-)-8'-epi-larreatricin, meso-3,3'-didemethoxynectandrin B and the new compounds, (+)- and (-)-3,3'-didemethoxyverrucosins. Following synthesis of each in either racemic or meso form, and chiral HPLC separation of the antipodes of the racemates, it was established that naturally occurring (-)-larreatricin and (-)-8'-epi-larreatricin were present in 92 and 98% enantiomeric excess, respectively, whereas 3,3'-didemethoxyverrucosin was essentially racemic and 3,3'-didemethoxynectandrin B was in the meso-form. The evidence suggests that formation of these lignans occurs under regiospecific, rather than stereoselective, coupling control. This contrasts with laccase-catalyzed "random" coupling of E-p-anol in vitro which generates the corresponding racemic 8-8', 8-3' and 8-O-4' linked dimeric moieties.