Chemoenzymatic Total Synthesis of (+)- & (−)-cis-Osmundalactone

•A novel, very concise stereoselective total synthesis of both enantiomers of cis-osmundalactone are presented.•The optimization of a one-pot two-step process merging biocatalytic transfer hydrogenation and oxygenation is disclosed.•The natural product is obtained in a purely catalytic fashion using three enzymes and one iridium catalyst.

Both optical antipodes of the cis-isomers of osmundalactone, a hydroxypyranone natural product and core structure of the angiopterlactones, have been synthesized from acetylfuran in only three steps through a redox cascade utilizing oxidoreductases and transition metal catalysis in a concerted fashion. The key step in this fully catalytic strategy is the enzyme-mediated Achmatowicz reaction via selective furan oxygenation to furnish the pyran core structure.

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