Synthetic Studies Towards Antimicrobial Therapeutic Agents : Aspterric Acid and Malacidin A

Abstract

Aspterric acid (11) is an unusual C15/C9 annulated daucane sesquiterpenoid originally isolated from the filamentous soil fungi Aspergillus terreus. Aspterric acid (11) exhibits potent microbial activity against DHAD (IC₅₀ = 0.31-0.50 μM) through a novel mode of action, which causes the inhibition of root development and plant growth. The promise held by 11 as a novel herbicidal agent and its unique structural complexity makes it an appealing target for total synthesis. Herein, the development of an asymmetric synthetic strategy towards aspterric acid (11) is described. The initial synthetic analysis focused on the construction of α-hydroxyacid 130 from triol 152. Bicycle 168 was smoothly transformed to trans-diol 193 in a four step sequence. Unfortunately, the assemblage of the THF ring through the C-H activation of 193 could not be effected, despite extensive studies.....