ABSTRACT
The first total synthesis of (-)-mucosin (6), an unusual marine hydrindane natural product incorporating a prostaglandin-like submotif, has been achieved. As a result of the campaign, three of the four all-carbon stereocenters in the purported structure 1 have been revised. Of particular note is the excellent control over ß-chirality in conjugate addition to ester (-)-22 and the facial selectivity in the subsequent protonation of an intermediate silyl ketene acetal.
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).
Subject(s)
Biological Products/chemistry , Biological Products/pharmacology , Terpenes/chemistry , Terpenes/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Cell Line, Tumor , Hep G2 Cells , Humans , K562 Cells , Lipid Peroxidation/drug effects , Plant Extracts/chemistry , Plant Extracts/pharmacology , Reactive Oxygen Species/metabolism , StereoisomerismABSTRACT
The first total synthesis aimed at the naturally occurring eicosanoid bicycle mucosin is reported. A practical route has been devised allowing the issues relating to the previous assignment of stereochemistry to be examined. X-ray crystallography was performed on a late stage intermediate to pinpoint the topological relationship displayed by the featured bicyclo[4.3.0]non-3-ene scaffold.
