Discovery and Total Synthesis of Seco-acorane Sesquiterpenoids from Chloranthus holostegius: Determination of Absolute Configuration and Spontaneous Acetalization

Shimianoids A–C, rare nor-acorane sesquiterpenoid (<b>1</b>) and aromatic <i>seco</i>-acoranes (<b>2</b>/<b>3</b>) featuring an aldehyde group, along with their spontaneous acetalization products with methanol-<i>d</i>₄ (<b>2a</b>/<b>3a</b>), were isolated and elucidated from Chloranthus holostegius var. shimianensis. The undetermined absolute configurations of the flexible side chain and intriguing spontaneous acetalization of compounds <b>2</b>/<b>3</b> prompted our total synthesis study.

Ultimately, compounds <b>2</b>/<b>3</b> and their acetalization products with methanol-<i>d</i>₄ (<b>2a</b>/<b>3a</b>) and CH₃OH (<b>2b</b>/<b>3b</b>) were synthesized via a redox-relay Heck reaction of 4-tolylboronic acid with (±)-sulcatol, followed by oxidation and acetalization. The absolute configurations of C7/10 at the flexible side chain were determined by Mosher’s and ECD methods of the synthetic intermediate, and the spontaneous reversible acetalization was confirmed.