Organic Letters 2013-07-05

Asymmetric synthesis of both enantiomers of arteludovicinolide A.

Andreas Kreuzer, Sabine Kerres, Thomas Ertl, Hannelore Rücker, Sabine Amslinger, Oliver Reiser

Index: Org. Lett. 15(13) , 3420-3, (2013)

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Abstract

The first total synthesis of either enantiomer of Arteludovicinolide A and their biological evaluation is reported, featuring a new strategy for the asymmetric construction of γ-butyrolactones with stereogenic side chains in the 4-position. Starting from the renewable resource methyl 2-furoate, the sesquiterpene lactone was synthesized in 9 steps and 4.8% overall yield via an asymmetric cyclopropanation and two diastereoselective nucleophile additions making use of a donor-acceptor-cyclopropane-lactonization cascade. At noncytotoxic concentrations (≤10 μM) (+)-1 was found to have a 15 times higher anti-inflammatory activity (4.87 ± 1.1 μM) than previously reported for concentrations of ≥45 μM.