Total Synthesis of BE-43472B

Key words

antibiotics - anthraquinone natural products - pinacol rearrangement - Diels–Alder cycloaddition

Significance

The aromatic polyketide BE-43472B was isolated from a marine Streptomyces species and was shown to exhibit significant activity against several drug-resistant bacterial strains. Moreover, its unprecedented structure includes two anthraquinones linked through a highly hindered carbon–carbon bond as well as five contiguous stereocenters. The strategy reported by ­Suzuki and co-workers relies on a highly efficient pinacol rearrangement to form the key C–C bond between the two anthraquinone monomers.

Comment

The synthesis starts with lithiation of bromonaphthalene B, followed by addition to ketone A. The resulting tertiary alcohol C was treated with triflic acid to induce a pinacol rearrangement to produce ketone D. Construction of the tetra­hydrofuran ring proceeded via acetal E followed by methylation using Me₃Al. Oxidation of F and subsequent quinone Diels–Alder reaction with diene G delivered anthraquinone H. This intermediate was converted into the natural product (±)-BE-43472B via epoxide J.