Synthesis, Biological Investigation, and Structural Revision of Sielboldianin A

  • J Nat Prod. 2018 Apr 27;81(4):1007-1013. doi: 10.1021/acs.jnatprod.8b00020.
Renate Kristianslund  1 ,  Marius Aursnes  1 ,  Jørn E Tungen  1 ,  Carl H Görbitz  2 ,  Trond V Hansen  1
Affiliations
  • 1. School of Pharmacy, Department of Pharmaceutical Chemistry , P.O. Box 1068 Blindern, University of Oslo , N-0316 Oslo , Norway.
  • 2. Department of Chemistry , P.O. Box 1033 Blindern, University of Oslo , N-0315 Oslo , Norway.
PMID: 29553260 DOI: 10.1021/acs.jnatprod.8b00020
Abstract

The two ar-bisabol sesquiterpenoids (+)-sielboldianin A (1) and (+)-sielboldianin B (2) were isolated from the stem bark of the plant Fraxinus sielboldiana and belong to a medicinally interesting class of natural products used in traditional Chinese medicine. Herein the total synthesis of the proposed structure of (+)-sielboldianin A (1) is reported using an organocatalyzed enantioselective bromolactonization protocol. X-ray analysis of a key intermediate together with specific rotation values and NOESY data of the synthesized product enabled the revision of the absolute configuration of the natural product (+)-sielboldianin A to (7 R,10 R). Studies on the antioxidant effects using two cell-based assays were conducted. These studies revealed that the enantiomer of 1 exhibited antioxidant effects with IC50 values of 18 ± 3 μM in a cellular lipid peroxidation antioxidant activity assay. Moreover, (-)-1 showed strong protective effects against Reactive Oxygen Species in a cell-based antioxidant activity assay (IC50 = 31 ± 5 μM). In addition, the two ar-sesquiterpenoids (-)-boivinianin B and (-)-gossoronol showed no effect in either assay. No cytotoxic activity in the K562 Cancer cell line was observed for the three sesquiterpenoids tested (IC50 > 50 μM).