Synthesis of the C1 to C13 tetrahydropyranyl-resorcylate core of paecilomycin B

A d-Glucose derived tetrahydropyran was converted into the C1 to C13 tetrahydropyranyl-resorcylate core of paecilomycin B in seven steps. Key transformations included the synthesis of a diketo-ester dioxinone, which upon thermolysis underwent a retro-hetero-Diels-Alder fragmentation to generate an acyl ketene. This was subsequently trapped by a secondary alcohol affording a triketo-ester, which was efficiently aromatized to produce the advanced resorcylate intermediate.