De Novo Asymmetric Approach to Aspergillide‐C: Synthesis of 4‐epi‐seco‐Aspergillide‐C

Abstract

AbstractAn asymmetric approach toward the synthesis of the marine natural product aspergillide‐C has been developed. The convergent asymmetric synthesis uses two asymmetric Noyori transfer hydrogenations to enantioselectively prepare the two key fragments, aC‐1 toC‐7 pyranone fragment and aC‐8 toC‐14β‐keto‐sulfone fragment. The absolute stereochemistry of the pyranone fragment was established by a Noyori reduction ofβ‐furylketoester to form a furyl alcohol. An Achmatowicz rearrangement was used to stereoselectively convert the furyl alcohol in to the key pyranone fragment. The absolute stereochemistry of theβ‐keto‐sulfone fragment was established by a Noyori reduction of an ynone to form a propargyl alcohol. An alkyne zipper isomerization was used to stereospecifically convert the propargyl alcohol in to theβ‐keto‐sulfone fragment. Finally, a Pd‐catalyzedC‐glycosylation was used to diastereoselectively couple the two fragments, which when combined with a reduction and Julia‐Kocienski type elimination formed a protected variant of the 4‐epi‐seco‐acid of aspergillide‐C.