The chemistry of fungi. Part 74. Synthesis of (±)-5-butyl-6,8-dihydroxy-3-pentyl-3,4-dihydroisocoumarin

Abstract

The title compound (1; R¹= Buⁿ, R²= H), which corresponds to the (+)-dihydro-derivative of fusamarin (2), a metabolite of an unidentified species of Fusarium, has been synthesised. (2-Butyl-3,5-dimethoxyphenyl)acetic acid (3; R¹= OH, R²= Buⁿ) was obtained from ethyl 3,5-dimethoxyphenylacetate by way of the corresponding 2-formyl derivative (3; R¹= OEt, R²= CHO). Reaction of the acid chloride (3; R¹= Cl, R²= Buⁿ) with pentylmagnesium bromide furnished 1-(2-butyl-3,5-dimethoxyphenyl)heptan-2-one (4; Ru = Buⁿ), which was reduced to the alcohol (5; R¹= H, R²= Buⁿ). Formylation of the acetate (5; R¹= Ac, R²= Buⁿ), followed by oxidation and hydrolysis of the ester residue, gave (±)-5-butyl-3-pentyl-6,8-dimethoxy-3,4-dihydroisocoumarin (1; R¹= Buⁿ, R²= Me), which was demethylated to (1; R¹= Buⁿ, R²= H). In model experiments (±)-6,8-dihydroxy-3-pentyl-3,4-dihydroisocoumarin (1; R¹= R²= H) and related derivatives, together with associated isochromans of type (7), have been synthesised.