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Total Synthesis of Amphidinolide X

MPS-Authors
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Lepage,  Olivier
Research Department Fürstner, Max-Planck-Institut für Kohlenforschung, Max Planck Society;

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Kattnig,  Egmont
Research Department Fürstner, Max-Planck-Institut für Kohlenforschung, Max Planck Society;

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Fürstner,  Alois
Research Department Fürstner, Max-Planck-Institut für Kohlenforschung, Max Planck Society;

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Citation

Lepage, O., Kattnig, E., & Fürstner, A. (2004). Total Synthesis of Amphidinolide X. Journal of the American Chemical Society, 126(49), 15970-15971. doi:10.1021/ja044130+.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000F-973D-5
Abstract
A concise total synthesis of the cytotoxic marine natural product amphidinolide X (1) is described. A key step of the highly convergent route to this structurally rather unusual macrodiolide derivative consists of a newly developed, highly syn selective formation of allenol 6 by an iron-catalyzed ring opening reaction of the enantioenriched propargyl epoxide 5 (derived from a Sharpless epoxidation) with a Grignard reagent. Allenol 6 was then cyclized with the aid of Ag(I) to give dihydrofuran 7 containing the (R)-configured quarternary sp3 chiral center at C19 of the target. The anti-configured chiral centers at C10 and C11 were formed by the palladium-catalyzed, Et2Zn-promoted addition of propargyl mesylate 12 to the functionalized aldehyde 11. The key fragment coupling at the C13−C14 bond was achieved by the “9-MeO-9-BBN” variant of the alkyl-Suzuki reaction. Finally, the 16-membered macrodiolide ring was formed by a Yamaguchi esterification/lactonization strategy.