Synthesis of larreantin, a cytotoxic naphthoquinonoid sesquilignan from Larrea tridentata

Abstract

Larreantin [8-(4-hydroxy-3-methoxyphenyl)-6-(4-hydroxy-3-methoxybenzyl)-2-methoxy-7-methyl-naphthalene-1,4-dione]1, a biogenetically unique cytotoxic naphthoquinonoid sesquilignan has been synthesized by a convergent route. The key intermediate was 4,5-dihydro-2-(5,7-diisopropoxy-1methoxy-2-naphthyl)-4,4-dimethyloxazole 14 which was elaborated by treatment with 4-isopropoxy-3-methoxyphenylmagnesium bromide 26 and the product of this reaction was lithiated and allowed to react with 4-isoproproxy-3-methoxybenzaldehyde 28. Subsequent steps then gave larreantin 1.