I Convergent Asymmetric Synthesis of (+)-Aureothin Employing an Oxygenase-Mediated Resolution Step

摘要

Aureothin (1) is an unusual polyketide metabolite of Strepto-myces thioluteus that is endowed with antitumor, antifungal, antiparasitic, and pesticidal activities (Scheme 1). Recent studies also demonstrated that 1 combines high efficiency and selectivity against trypanosome strains. The molecule accumulates in a dense framework a stereodefined 1,3-diene with a 4-nitroaryl group and a chiral tetrahydrofuran moiety connected to the a'-methoxy-γ-pyrone scaffold. As a representative of rare natural nitro-substituted pyrones, the structure of 1 is closely related to other bioactive polypropi-onates, such as (+)-spectinabilin (also known as neoaureo-thin, 2), their respective isomers (—)-alloaureothin (3) and (-)-arabilin (4), and cycloisomer SNF4435C (5) Only recently has rac-1 become the target of total syntheses, along with a renewed general interest in unsaturated poly-proprionates of this class. The synthetic route to (+)-1 is paved with hurdles, such as the stereodefinition and the conservation of the 1,3-diene and the stereocenter at C7. Indeed, both were reported to be prone to isomerization under sunlight and to epimerization in an acidic or basic environment.