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Updated: Dec 2, 2025

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Published on: June 13, 2022
Total Syntheses of (±)-Melicolones A and B
Zhipeng Wang1, Stephen F Martin1
1Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712, United States.
Abstract:
The first total syntheses of (±)-melicolones A and B, which have a unique and densely functionalized framework derived from a rearranged prenylated acetophenone, were accomplished in 12.3% combined overall yield. The concise and divergent synthesis of these two natural products, which were isolated in racemic form, was achieved in a longest linear sequence requiring only 9 steps (11 total steps) and 8 isolated intermediates using commercially available starting materials. This approach, which might enable access to all tetracyclic melicolones, features the highly regioselective (16:1) and diastereoselective (15:1) dipolar cycloaddition of a carbonyl ylide generated by the unusual cyclization of a rhodium carbene with the carbonyl oxygen atom of an aliphatic aldehyde. This cycloaddition proceeds with dominant steric control to give a highly functionalized oxabicycloheptane core. Stereoselective enolate alkylation led to a prenylated intermediate that underwent an intramolecular aldol reaction to give the penultimate tricyclic intermediate. Tandem epoxidation of the pendant prenyl group followed by a regioselective, acid-catalyzed cyclization delivered (±)-melicolones A and B.
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