Flexible Total Synthesis of (±)-Aureothin, a Potent Antiproliferative Agent

Amenable to late-stage preparation of analogues, a flexible and convergent total synthesis of (±)-aureothin is presented. The strategy was based on a desymmetrization of α,α′-dimethoxy-γ-pyrone by a process combining 1,4-addition and alkylation of vinylogous enolate to stereoselectively reach the ba...

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Bibliographic Details
Published in:Journal of organic chemistry 2016-06, Vol.81 (12), p.5190-5201
Main Authors: Henrot, Matthias, Jean, Alexandre, Peixoto, Philippe A, Maddaluno, Jacques, De Paolis, Michaël
Format: Article
Language:English
Subjects:
Alkylation
Antifungal Agents - chemical synthesis
Catalysis
Chemical Sciences
Chromones - chemical synthesis
Cycloaddition Reaction
Furans - chemical synthesis
Magnetic Resonance Spectroscopy
Organic chemistry
Oxidation-Reduction
Palladium
Stereoisomerism
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Summary:Amenable to late-stage preparation of analogues, a flexible and convergent total synthesis of (±)-aureothin is presented. The strategy was based on a desymmetrization of α,α′-dimethoxy-γ-pyrone by a process combining 1,4-addition and alkylation of vinylogous enolate to stereoselectively reach the backbone of the target. Palladium-catalyzed cyanation of an elaborated and isomerizable E,Z dienyl motif followed by Pinner cyclization enabled the construction of the tetrahydrofuran motif while a first approach based on a late-stage oxidation was unsuccessful.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.6b00878