First total synthesis of the antifungal antibiotic thiobutacin

The first total synthesis of thiobutacin, a butanoic acid with antifungal activity recently isolated from the culture broth of a soil actinomycete, Lechevalieria aerocolonigenes strain VK-A9, is described. The five-step procedure involves readily available and cheap starting materials and can easily be transposed to the large scale. Fungal growth inhibition of thiobutacin is mediated by the pH of the growth medium. Maximum inhibitory activity was obtained between pH 6 and 7.