2. Academic Validation
  3. Stereoselective Synthesis of Xylodonin A and 22-Hydroxyxylodonin A and Discovery of Analogues with Cytotoxic Activity

Stereoselective Synthesis of Xylodonin A and 22-Hydroxyxylodonin A and Discovery of Analogues with Cytotoxic Activity

  • J Nat Prod. 2024 Apr 26;87(4):884-892. doi: 10.1021/acs.jnatprod.3c01150.
Yue-Cheng Wu 1,  Guang-Sen Xu 2,  Hui-Jing Li 1 2,  Yan-Chao Wu 1 2
Affiliations

Affiliations

  • 1 Weihai Marine Organism & Medical Technology Research Institute, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150006, People's Republic of China.
  • 2 Weihai Key Laboratory of Active Factor of Marine Products, Weihai Marine Organism & Medical Technology Research Institute, Harbin Institute of Technology, Weihai 264209, People's Republic of China.
PMID: 38408342 DOI: 10.1021/acs.jnatprod.3c01150
Abstract

The first and stereoselective synthesis of xylodonin A and 22-hydroxyxylodonin A, two drimane-type sesquiterpenoid natural products, was developed from the readily available (+)-sclareolide. This route features an allylic oxidation and acid-promoted dehydration for construction of the key intermediate 6-hydroxyisodrimenin. Representative analogues were synthesized, and their previously unknown bioactivities were revealed after biological evaluation. The analogue 19a exhibited cytotoxic activity against liver Cancer HepG2 cells (IC50: 8.8 vs 5.9 μM) that was comparable to that of the clinical Anticancer drug etoposide with lower toxicity to normal liver HL7702 cells (IC50 > 100 μM).

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