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

Abstract

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.