This work reports the development of a chiral-pool-based strategy for the asymmetric synthesis of trans-syn-fused drimane meroterpenoids. Two enabling features in the synthesis are the strategic use of an acid-mediated C9-epimerization of sclareolide to generate the general trans-syn-fused architecture of these natural products and the ability to perform regioselective C-H oxidations on different key synthetic intermediates at their C3 position by relying on a small pool of P450BM3 biocatalysts. By combining these features with contemporary annulation methodologies, the first total syntheses of polysin, N-acetyl-polyveoline, chrodrimanin C and verruculide A could be realized. The route disclosed herein lays the foundation for future synthetic access to other unusually-cyclized meroterpenoids and their unnatural derivatives to facilitate a more thorough investigation into their pharmacology.