Abstract
The first syntheses of the isomeric dioxafenestrene natural products (−)-asperaculin A and (−)-penifulvin D are reported. Each target is formed selectively by choice of oxidant in a final divergent bioinspired Baeyer–Villiger (BV) reaction. Density functional theory calculations reveal that electrostatic interactions between the oxidant leaving group and the lactone motif accounts for a reversal of selectivity with H2O2/H3O+ compared to peracids. Synthetic features include forging the polycyclic carbon framework with a diastereoselective meta-photocycloaddition biased by an ether substituent at the aryl α-position. The encumbered tertiary alcohol was installed by cyanation of a ketone intermediate followed by nonaqueous hydrolysis of the resulting delicate cyanohydrin.
Highlights
The first syntheses of the isomeric dioxafenestrene natural products (−)-asperaculin A and (−)-penifulvin D are reported
Biosynthesis remains a rich source of inspiration for discovering new strategies and tactics in chemical synthesis.[1,2]
We considered the possibility that asperaculin A and penifulvin D share a biosynthetic origin via a BV reaction, and, that chemical synthesis of both structures through a divergent biomimetic BV reaction was a feasible prospect
Summary
The first syntheses of the isomeric dioxafenestrene natural products (−)-asperaculin A and (−)-penifulvin D are reported. We show that a simple change of oxidant reverses the selectivity in favor of the isomeric penifulvin D, a first chemical synthesis of a ringhydroxylated penifulvin. Optimization of solvent, reaction time, and light source clarified that irradiation in pentane with 300 nm light until 75% conversion (∼70 h) gave the highest yield, 24% of 9a (measured by 1H NMR spectroscopy using an internal standard).
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