Title: A Short Total Synthesis of Aureothin and NAcetylaureothamine Mikkel F' Jacobsen, John E' Moses, Robe
1A 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
2Author
- 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
3Introduction
- 1. Bioactivity Structure
- 2. Retrosynthesis
- 3.Result Discussion
- 4.Conclusion
4Bioactivity
- 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.
5Structure
- 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
6Suzuki coupling
7Cross metathesis
8Retrosynthesis
9Preparation of aldehyde 9
10Lemieux-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.
11Prepare 8 by Pd-coupling
12Prepare 8 by Pd-coupling (Mechanism)
13TMM 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.
14Cross metathesis
15Cross metathesis of alkenyl boronic ester with
olefin (I)
16Cross metathesis of alkenyl boronic ester with
olefin (II)
17Suzuki coupling
18Suzuki coupling (I)
19The Way of Synthesize Compound 19
20Suzuki coupling (II)
21Suzuki coupling (III)
22Suzuki 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
23Synthesize 1 by Negish-type Coupling
24Synthesis of Compound 2
25Conclusion
- 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.
26Conclusion
- 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.
27Conclusion
- 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.