A Short Total Synthesis of Aureothin and NAcetylaureothamine Mikkel F' Jacobsen, John E' Moses, Robe

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A Short Total Synthesis of Aureothin and
N-AcetylaureothamineMikkel F. Jacobsen, John
E. Moses, Robert M. Adlington, and Jack E.
BaldwinChemistry Research Laboratory,
UniVersity of Oxford.ORGANIC LETTERS2005
Vol. 7, No. 4, 641-644
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Author

• Professor Sir Jack Baldwin is the Waynflette
  Professor of Organic Chemistry at the University
  of Oxford, a position he has held for over 20
  years. The Baldwin Group is home to a wide array
  of research in bio-organic and synthetic organic
  chemistry

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Introduction

• 1. Bioactivity Structure
• 2. Retrosynthesis
• 3.Result Discussion
• 4.Conclusion

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Bioactivity

• Aureothin 1 has been found in the mycelia of
  several actinomycetes, and possesses antitumor,
  antifungal, and pesticidal activities.
• N-Acetylaureothamine 2, isolated from
  Streptomyces netropsis, has been shown to be a
  highly selective and potent agent against
  Helicobacter pylori, a common cause of chronic
  gastritis.

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Structure

• Aureothin 1 and N-acetylaureothamine 2 are two
  unusual natural products, both featuring a rare
  nitroaryl group and a highly substituted
  conjugate diene system.
• The KEY step
• Palladium coupling (Suzuki coupling )
• Rethenium cross-metathesis

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Suzuki coupling
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Cross metathesis
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Retrosynthesis
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Preparation of aldehyde 9
10
Lemieux-Johnson Reaction
Osmium reagents When alkenes are oxidized with a
mixture of OsO4 and NaIO4 (Lemieux-Johnson
Reagent), oxidative cleavage leads to aldehyde
and ketone products.
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Prepare 8 by Pd-coupling
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Prepare 8 by Pd-coupling (Mechanism)
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TMM of Pd-Catalysed 33 Cycloaddition Reactions

• A novel approach to enantiomerically pure
  piperidines has been recently developed through
  an unusual Pd-catalysed 33 cycloaddition
  reaction. Specifically, in situ generated Pd-TMM
  (TMMtrimethylenemethane) reagents were found to
  add to aziridines efficiently and with retention
  of stereochemistry at the aziridine stereogenic
  centre.

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Cross metathesis
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Cross metathesis of alkenyl boronic ester with
olefin (I)
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Cross metathesis of alkenyl boronic ester with
olefin (II)
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Suzuki coupling
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Suzuki coupling (I)
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The Way of Synthesize Compound 19
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Suzuki coupling (II)
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Suzuki coupling (III)
22
Suzuki coupling (IV)
.
Suzuki couplings of alkenyl dibromides are known
to occur with high trans-selectivity however,
the choice of base is sometimes crucial in order
to obtain only the monoalkylated product
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Synthesize 1 by Negish-type Coupling
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Synthesis of Compound 2
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Conclusion

• The author developed short total syntheses
  of()-aureothin 1 and ()-N-acetylaureothamine 2
  affording the natural products in 23 and 18
  overall yield from known 10, respectively.

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Conclusion

• The key steps involved in the synthesis are the
  construction of the tetrahydrofuran motif using a
  palladium catalyzed cycloaddition and the
  ruthenium-catalyzed cross-metathesis reaction of
  an alkenyl boronic ester.

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Conclusion

• Further efforts in authors laboratories are now
  being directed toward the implementation of their
  developed synthetic methodology for the synthesis
  of spectinabilin 3, and its subsequent biomimetic
  conversion to 4 and 5.