Trans-syn-fused drimane meroterpenoids are unique natural products that arise from contra-thermodynamic polycyclizations of their polyene precursors. Herein we report the first total syntheses of four trans-syn-fused drimane meroterpenoids, namely polysin, N-acetyl-polyveoline, chrodrimanin C and verruculide A in 7–18 steps from sclareolide. The trans-syn-fused drimane unit is accessed through an efficient acid-mediated C9 epimerization of sclareolide. Subsequent applications of enzy-matic C–H oxidation and contemporary annulation methodologies install the requisite C3 hydroxyl group and enable rapid gen-eration of structural complexity to provide concise access to these natural products.
Supporting Information for A Unified Strategy to Access Trans-Syn-Fused Drimane Meroterpe-noids: Chemoenzymatic Total Syntheses of Polysin, N-Acetyl-Polyveoline and the Chrodrimanins
Experimental details, analytical data, 1H and 13C NMR data (PDF)