The First Synthesis of the ABC-Ring System of ‘Upenamide

The first synthetic route to the spirooxaquinolizidinone core (ABC core) of the macrocyclic marine alkaloid ‘upenamide (<b>1</b>) has been developed. All five stereocenters were introduced with complete stereocontrol. The hydroxyl group at C-11 was introduced by a regio- and stereoselective SeO<sub>2</sub>-mediated allylic oxidation. The spirocyclic skeleton was formed by a stannous chloride induced deacetalization−bicyclization procedure. Further stereocenters were introduced by an enzymatic desymmetrization and by incorporation of an (<i>S</i>)-malic acid derived building block.