Discovery and Total Synthesis of Seco -acorane Sesquiterpenoids from Chloranthus holostegius : Determination of Absolute Configuration and Spontaneous Aceta
Shihao Cheng, Jie Wen, Houli Jiang, Yuhang Zhou, Yi Zhu, Danyang Zhang, Lingyi Kong, Jun LuoAbstract
Shimianoids A–C, rare nor-acorane sesquiterpenoid (1) and aromatic seco-acoranes (2/3) featuring an aldehyde group, along with their spontaneous acetalization products with methanol-d4 (2a/3a), were isolated and elucidated from Chloranthus holostegius var. shimianensis. The undetermined absolute configurations of the flexible side chain and intriguing spontaneous acetalization of compounds 2/3 prompted our total synthesis study. Ultimately, compounds 2/3 and their acetalization products with methanol-d4 (2a/3a) and CH3OH (2b/3b) 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. Finally, a library of 26 aromatic seco-acorane sesquiterpenoids was constructed for bioactivity screening.