Asymmetric Synthesis of Both Enantiomers of Arteludovicinolide A

作者：Kreuzer Andreas; Kerres Sabine; Ertl Thomas; Ruecker Hannelore; Amslinger Sabine; Reiser Oliver^*

来源：Organic Letters, 2013, 15(13): 3420-3423.

DOI：10.1021/ol401473v

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 gamma-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 (%26lt;= 10 mu M) (+)-1 was found to have a 15 times higher anti-inflammatory activity (4.87 +/- 1.1 mu M) than previously reported for concentrations of %26gt;= 45 mu M.

• 出版日期2013-7-5