Total Synthesis of Aureothin and N-Acetylaureothamine

doi:10.1055/s-2005-865349

Synfacts 2005(0): 0009-0009
DOI: 10.1055/s-2005-865349

Synthesis of Natural Products and Drugs

Total Synthesis of Aureothin and N-Acetylaureothamine

Contributor(s): Philip Kocienski

M. F. Jacobsen, J. E. Moses, R. M. Adlington, J. E. Baldwin*
Oxford University, UK
A Short Total Synthesis of Aureothin and N-Acetylaureothamine
Org. Lett. 2005, 7: 641-644

Abstract

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Key words

[3+2] cycloaddition - cross-coupling - metathesis

Significance

<P>Aureothin is an unusual nitroaryl metabolite of Streptomyces netropis. It has antitumor, antifungal and pesticidal activity. N-Acetylaureothamine is active against Helicobacter pylori, the cause of chronic gastritis.</P>

Comment

<P>A remarkably short and efficient synthesis of ()-Aureothin (23% overall) features three Pd-catalyzed reactions and a Ru-catalyzed cross metathesis. The precipice of failure in the three Pd-catalyzed reactions was avoided by deft use of additives: In(acac)₃ for the [3+2] cycloaddition leading to tetrahydrofuran B; TlOEt for the Suzuki cross-coupling to form E; the highly hindered ligand t-Bu₃P for the final Negishi cross-coupling.</P>

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