Synthesis of Exiguamine A

doi:10.1055/s-0028-1087689

Synfacts 2009(3): 0233-0233
DOI: 10.1055/s-0028-1087689

Synthesis of Natural Products and Potential Drugs

Synthesis of Exiguamine A

Contributor(s):Philip Kocienski, Indu Dager

M. Volgraf, J.-P. Lumb, H. C. Brastianos, G. Carr, M. K. W. Chung, M. Münzel, A. G. Mauk, R. J. Andersen*, D. Trauner*
University of California, Berkeley, USA; University of British Columbia, Vancouver, Canada; Ludwig-Maximilians-Universität München, Germany
Biomimetic Synthesis of the IDO Inhibitors Exiguamine A and B
Nat. Chem. Biol. 2008, 4: 535-537

Abstract

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Key words

exiguamines - Henry reaction - Hemetsberger indole cyclization - oxa-6π-electrocyclization - biomimetic synthesis

Significance

Exiguamine A is isolated from the marine sponge Neopetrosia exigua and is a potent inhibitor of indoleamine-2,3-dioxygenase, which in turn metabolizes tryptophan. This biomimetic synthesis relies on a cascade sequence involving intramolecular nucleophilic attack of a tertiary amine onto an o-quinone and tautomerization followed by an oxa-6π-electrocyclization (I → exiguamine A).

Comment

The phenol resulting from benzyl deprotection of F was subjected to salcomine oxidation which gave a 2.5:1 mixture of the regioisomeric o- and p-quinones, respectively (F → G). Upon treatment with 10 equivalents of AgO, I afforded exiguamine A, but with 20 equivalents of AgO exiguamine B was the main product. Treatment of exiguamine A with excess of AgO failed to give exiguamine B.

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