Synthesis of (+)-11-Hydroxyabieta-2,8,11,13-tetraen-1-one

Treatment of methyl (+)-11-oxo-13β-abieta-8-en-18-oate with copper(II) bromide and lithium bromide afforded the corresponding phenol derivative, which was methylated to methyl 11-methoxyabieta-8,11,13-trien-18-oate (7). The same compound was also prepared from methyl (+)-7,11-dioxo-13β-abieta-8-en-18-oate via methyl 11-hydroxy-7-oxoabieta-8,11,13-trien-18-oate, its methyl ether, and methyl 11-methoxyabieta-6,8,11,13-tetraen-18-oate. The Grignard reaction of 7 with phenylmagnesium bromide followed by treatment with lead tetraacetate and subsequent oxidation with selenium dioxide afforded 11-methoxy-19-norabieta-4(18),8,11,13-tetraen-3α-ol (12), which was converted to 11-methoxy-19-norabieta-8,11,13-trien-3-one (20) by catalytic hydrogenation, Jones oxidation, and isomerization. The compound 20 was also obtained by Birch reduction of 11-methoxy-19-norabieta-4,8,11,13-tetraen-3-one prepared from 12 via 11-methoxy-19-norabieta-4,8,11,13-tetraen-3α-ol. Subsequently, the compound 20 was transformed to 11-methoxyabieta-1,8,11,13-tetraen-3-one (27) by a series of reactions: acetalization, demethylation, hydrolysis, acetylation, bromination, dehydrobromination, and methylation. Finally, the compound 27 was converted to the title compound, (+)-11-hydroxyabieta-2,8,11,13-tetraen-1-one (1), by oxidation with alkaline hydrogen peroxide, heating with hydrazine hydrate, Jones oxidation, and demethylation. Although the synthetic (+)-1 was shown to be different from natural shonanol, the spectral analyses of the synthetic structural isomers showed the structure of shonanol to be 12-hydroxyabieta-2,8,11,13-tetraen-1-one.