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9-Step synthesis of (-)-larikaempferic acid methyl ester enabled by skeletal rearrangement
Mario E Rivera1, Lei Li1, Aditya Kolisetti1
1Department of Chemistry, Emory University, Atlanta, GA 30022, USA. mingji.dai@emory.edu.
Abstract:
We report here a concise synthesis of the anti-tumor-promoting (-)-larikaempferic acid methyl ester, a novel and rearranged abietane-type diterpene natural product containing a unique tetracyclic skeleton with a trans-hydrindane, an oxabicyclo[3.2.1]octane, and six stereogenic centers. Our synthesis starts with the cheap and abundant abietic acid and features an oxidative C-C bond cleavage followed by a transannular aldol reaction to skeletally rearrange the 6-6-6 tricyclic carbon skeleton of abietic acid to the desired 6-5-7 tricyclic carbon skeleton and an intramolecular oxa-Michael addition to form the oxa bridge. This skeletal rearrangement strategy enabled us to synthesize (-)-larikaempferic acid methyl ester in 9 steps.
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