Curvularin. Part VI. The preparation of some acylated dimethoxyphenylacetic acids and related compounds

Abstract

The substituted octanoic acids HO2C·[CH2]5·CHY·Me(Y = Br, OH, OAc, and OMe) are prepared from 7-oxo-octanoic acid. The acylation of methyl 3,4-dimethoxyphenylacetate with hexanoic acid (using polyphosphoric acid) or with octanoyl chloride (using aluminium chloride or silver perchlorate) gives the expected methyl 2-acyl-4,5-dimethoxyphenylacetates. Similar acylation reactions employing the substituted octanoic acids (or the corresponding acid chlorides) are successful and give similar 2-acyl derivatives only when the acyl group is 7-oxo-, 7-hydroxy-, or 7-acetoxy-octanoyl. Hydrogenation of methyl 4,5-dimethoxy-2-(7-oxo-octanoyl)phenylacetate gives 1-(6-hydroxyheptyl)-6,7-dimethoxyisochroman-3-one while treatment with ethanolic alkali in the presence of air gives 2-hydroxy-6,7-dimethoxy-3-(5-oxohexyl)-1,4-naphthaquinone. Methyl 3,5-dimethoxyphenylacetate reacts with octanoyl chloride and aluminium chloride to give 3,5-dimethoxy-2-octanoylphenylacetic acid but the reactions with the substituted octanoic acids (or their acid chlorides) using the above conditions fail to give acylated products. Acylation does occur however with 7-hydroxyoctanoic acid in trifluoracetic anhydride with the formation of methyl 2-(7-hydroxyoctanoyl)-3,5-dimethoxyphenylacetate. Hydrolysis of this ester gives the corresponding acid while hydrogenation gives 2-(7-hydroxyoctyl)-3,5-dimethoxyphenylacetic acid. Neither of these hydroxy-acids can be dehydrated to give the corresponding lactone and the synthesis of derivatives of curvularin by this route is therefore not possible.