Stereoselective total syntheses of the (±)-di-O-methyl ethers of agatharesinol, sesquirin-A, and hinokiresinol, and of (±)-tri-O-methylsequirin-E, characteristic norlignans of coniferae

Abstract

Total syntheses of the (±)-di-O-methyl ethers of the norlignans sequirin-A, agatharesinol, and hinokiresinol, and of (±)-Tri-O-methyl sequirin-E are described. p-Methoxyacetophenone was converted into p-methoxybenzoylethylene and thence into 4-(p-methoxybenzoyl)-2,2-dimethyl-1,3-dioxolan (13). The glycidic acid (15) was obtained from (13) by Darzens condensation with benzyl chloroacetate and hydrogenolysis of the resulting ester. Decarboxylation–rearrangement in hot acetone of the glycidic acid was stereoselective providing the desired diastereoisomer (17)(>80%) of 2,2-dimethyl-1,3-dioxolan-4-yl-(p-methoxyphenyl)acetaldehyde. Reaction of (17) with p-methoxybenzylidenetriphenylphosphorane gave trans- and cis-(±)-dimethylagatharesinol acetonides The trans-acetonide (19) was hydrolysed to (±)-dimethylagatharesinol (21); pyrolysis of the mixed orthoformate of the latter provided (±)-dimethylhinokiresinol. The cis-isomer (18) was hydrolysed and cyclised to yield (±)-dimethylsequirin-A. Reaction of the aldehyde (17) with 3,4-dimethoxybenzylidenetriphenylphosphorane, followed by acid-catalysed cyclisation, afforded (±)-trimethylsequirin-E, via the acetonide (20). An alternative approach to dimethylagatharesinol is discussed.