A Carbene Catalysis Strategy for the Synthesis of Protoilludane Natural Products
M Todd Hovey1, Daniel T Cohen1, Daniel M Walden2
1Department of Chemistry, Department of Phamacology, Center for Molecular Innovation and Drug Discovery, Northwestern University, 2145 Sheridan Rd, Evanston, IL, 60208, USA.
Abstract:
The Armillaria and Lactarius genera of fungi produce the antimicrobial and cytotoxic mellolide, protoilludane, and marasmane sesquiterpenoids. We report a unified synthetic strategy to access the protoilludane, mellolide, and marasmane families of natural products. The key features of these syntheses are 1) the organocatalytic, enantioselective construction of key chiral intermediates from a simple achiral precursor, 2) the utility of a key 1,2-cyclobutanediol intermediate to serve as a precursor to each natural product class, and 3) a direct chemical conversion of a protoilludane to a marasmane through serendipitous ring contraction, which provides experimental support for their proposed biosynthetic relationships.
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