Total Synthesis of (±)-Pisiferic Acid, Methyl (±)-Pisiferate, and (±)-Pisiferol

Acid catalyzed cyclization of 4-(3-isopropyl-4-methoxyphenethyl)-3,5,5-trimethyl-2-cyclohexen-1-one afforded 12-methoxyabieta-8,11,13-trien-2-one and its cis-isomer. Both compounds were further converted into 12-methoxyabieta-8,11,13-trien-2β-ol, which was treated with lead tetraacetate in the presence of iodine to yield 2β,20-epoxy-12-methoxyabieta-8,11,13-triene. Ether cleavage of the 2β,20-epoxy compound with acetyl p-toluenesulfonate, followed by catalytic hydrogenation, afforded 20-acetoxy-12-methoxyabieta-8,11,13-triene (23). This was then converted into methyl 12-methoxyabieta-8,11,13-trien-20-oate (27) via methyl 12-methoxy-7-oxoabieta-8,11,13-trien-20-oate. Demethylation of 27 with AlBr3–EtSH gave pisiferic acid, but with AlCl3–EtSH 27 was partially demethylated to give methyl pisiferate. The acetate 23 was also converted into pisiferol by demethylation and reduction.