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DOI: 10.1055/s-0028-1087689
Synthesis of Exiguamine A
Rezensent(en):Philip Kocienski, Indu DagerUniversity 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
Publikationsverlauf
Publikationsdatum:
19. Februar 2009 (online)
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.