The synthetic route in this work is based on the classical Friedel-Crafts strategy,
and began with 1,4-dimethoxybenzene (I), followed by alkylation and selective
demethylation of 2-methoxy function in 0x0-acid (3). The orthoformylation to
synthesize aldehyde (6) was based on the Reimer-Tieman reaction. Chain extension
of this aldehyde required methylation of the hydroxyl group and condensation with
pyruvic acid which afforded acid (8) in 85% yield. Two steps reduction process of this
acid led to diacid (1 1) in good yield. A direct "biscylisation" of (1 1) afforded diketone
(12) as the main product. This compound was converted to (1,8-DHA), 15, via an
aromatization process