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Studies toward Australifungin. A Synthesis Dilemma of Regioselective Keto–Enol Tautomerization

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journal contribution
posted on 04.02.2016 by David R. Williams, J. Cullen Klein, Lucas C. Kopel, Nhu Nguyen, Dean J. Tantillo
Studies have advanced a stereocontrolled pathway for the synthesis of australifungin. Elaboration of the trans-fused IMDA product 4 led to the cis-diol 15, which produced the α-hydroxyenone 19 upon oxidation. Computational studies on model systems indicate that the keto–enol tautomer shown for 19 is higher in energy than the keto–enol tautomer represented by the natural product 1. The reactivity of 19 does not permit mild isomerization and subsequent deprotection to yield 1. These findings raise new questions regarding the synthesis and bioactivity of australifungin and related natural products.