Search

The asymmetric allylation under the assistance of catalytic amounts of 3,3′-bis(2,4,6-triisopropylphenyl)-1,1′-binaphthyl-2,2′-diyl hydrogen phosphate (TRIP) allows the concise construction of the lignan scaffold from simple aldehydes and allylic bromides with full control of the two formed stereocenters. This young methodology has been employed to synthesize four naturally and pharmaceutically active lignans. Members of the dibenzylbutyrolactone, the tetraline, and the dibenzocyclooctadiene classes have been synthesized in 40–47% overall yield along four-step synthetic routes.

Methods for the preparation of phosphites and phosphates from chiral diols based on lignan backbones were developed. Four novel phosphites and one phosphate were synthesized and characterized. Sterically hindered diols showed diastereoselectivity in formations of phosphites, whereas non-hindered diols showed no selectivity.

The structures of the naturally occurring lignan hydroxymatairesinol (HMR) and TADDOL-like α -conidendrin-based chiral 1,4-diols (LIGNOLs) have been studied at DFT/B3LYP/TZVP level of theory, for the first time applying the density functional dispersion correction (DFT-D3) [1] and employing the BJ-damping (-D3(BJ)) [2] . This study establishes the necessity of treating the dispersion interactions properly in DFT optimizations. Several of the conformers received were not found in previous studies and the 4Ph4 structure received applying D3 is now published for the first time as a quantum chemically optimized structure.

The acid-catalyzed rearrangement of diaryl-dilactones, readily obtained by oxidation of ferulic acid derivatives, is examined as a synthesis route to aryltetralins. Two structures which have been proposed for the lignan, phyltetralin, are shown by synthesis of the two diastereomeric 1-veratryltetralins ( 3A ) and ( 3B ), to be untenable. Conidendrin has been converted to isolariciresinol tetramethyl ether ( 21 ) and comparison of empirical constants and spectra with those reported for phyltetralin strongly suggest that the lignan has the enantiomeric constitution ( 26 ).

An all trans 1-aryl-2-methoxycarbonyl tetralin-3-carboxylic acid synthesised in 32% overall yield can be converted, at will, to either dimethyl conidendrin or dimethyl retrodendrin in one step.