Preparation of acyltetronic acids using t-butyl acetothioacetate: total synthesis of the fungal metabolites carolic, carlosic, and carlic acids

Abstract

Dianions generated from S-t-butyl acetothioacetate (1) were alkylated with a variety of electrophiles at the γ-carbon centre. Treatment of the alkylated products with 2-hydroxy esters in the presence of silver(I) salts gave transesterified acetoacetate derivatives in good yields. These acetoacetates were cyclised efficiently to acyltetronic acid derivatives using tetrabutyl ammonium fluoride in THF solution at room temperature. By an appropriate choice of substituents the total syntheses of the fungal metabolite natural products carlosic, carolic, and carlic acids have been achieved.