Derivatives of the Lignan 7'-Hydroxymatairesinol with Antioxidant Properties and Enhanced Lipophilicity.

The lignan 7'-hydroxymatairesinol (1), extracted from the knotwoods of fir (Abies alba), spruce (Picea abies), and Douglas fir (Pseudotsuga menziesii), exhibited unexpected reactivity when esterification reactions were attempted on the hydroxy group at position C-7'. To circumvent the rapid intramolecular cyclization procedure, leading quantitatively to the lignan conidendrin (7), a simple strategy for 7'-esterification of 1 under mild conditions (three steps, up to 80% overall yield) was developed. Compared to hydroxymatairesinol (1) (log K'w = 1.49), the derivatives (2-5) had increased lipophilicity with log K'w > 3.1, as determined by a UHPLC method. Compounds 1-5 exhibited potent antioxidant properties in the same range as the standards ascorbic acid and α-tocopherol (IC50 = 20-25 μM) and higher than that of BHT using a DPPH radical-scavenging assay.