A Chiral-Pool-Based Strategy to Access trans-syn -Fused Drimane Meroterpenoids: Chemoenzymatic Total Syntheses of Polysin, N -Acetyl-polyveoline and the Chrodrimanins

作者：Fuzhuo Li, Hans Renata · 发表于：Journal of the American Chemical Society · 年份：2021 · DOI：10.1021/jacs.1c08696 · 被引用次数：59 · 研究领域：Marine Sponges and Natural Products、Synthetic Organic Chemistry Methods、Microbial Natural Products and Biosynthesis

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 enzymatic C–H oxidation and contemporary annulation methodologies install the requisite C3 hydroxyl group and enable rapid generation of structural complexity to provide concise access to these natural products.