As noted above, our synthetic strategy was predicated upon the ability of sclareolide (7) to undergo facile epimerization at its C8 and C9 positions. Prior report from Ohloff (Figure , inset) showed that treatment of 7 with mineral acid at room temperature could readily afford the C8-epimerized product 12 (8). Alternatively, the C9-epi product (9) was observed as the major product at elevated temperature, likely via elimination to the corresponding C8-C9 olefin, followed by re-protonation from the b-face at C8 and quenching of the C9 carbocation from the a-face by the pendant carboxylic acid. In our hands, this transformation could be routinely conducted on multigram scale with 95% yield. With the C9 stereocenter established, access to polysin and N-acetyl-polyveoline could be accomplished through selective C-H oxidation at C3 and the appendage of a pendant indole unit (Figure ). We envisioned introducing the former through enzymatic C-H hydroxylation and the latter through ring synthesis by leveraging the C12 carbonyl as a chemical handle. Adaptation of this idea to access the chrodrimanin series would necessitate the invention of a synthetic sequence to construct the C-ring pyran while also inverting the stereochemistry at C8. While the general pyran structure could be prepared via a one-carbon homologation, the stereoinversion at C8 was expected to be non-trivial as it would result in an A/B/C-ring connectivity that forces the B-ring to adopt the energetically-unfavored twist-boat conformation. Nevertheless, if this transformation could be realized, an efficient synthesis of chrodrimanin C would ensue through subsequent use of the C-ring lactone as a chemical handle in an aromatic annulation sequence. Finally, enzymatic conversion of 3 to 4 through a series of in vitro reactions has previously been reported by Matsuda, Abe and co-workers. Scheme 1. Chemoenzymatic total synthesis of polysin (1) and N-acetyl-polyveoline (2) via enzymatic C-H oxidation of 9.