Organic Letters
Letter
(acetonitrile employed for solubility of this substrate) to
provide morpholinone 18 in 41% yield (69% brsm) (crude
material was a 9:1 mixture of diastereomers, but only the major
diastereomer was isolated after chromatography). Reduction of
the bis-azide was accomplished via hydrogenation over Pd/C to
reveal morpholinone diamine 19 in 58% yield after reversed
phase chromatography. We found it to be essential to use
heterogeneous reduction conditions, as 18 is not stable to
extended treatment with PPh3; however, it is important to note
that the final product is stable to reversed phase chromatog-
raphy (0.1% TFA) and is stable to storage at room temperature
for several weeks without significant decomposition.
In addition to phenyl substituted derivative 19 we also
targeted allyl-functionalized morpholinone 21, as this moiety
contained a handle for future incorporation into the natural
product and could be reduced to provide the diamine required
for monanchocidin A. Analogous to the preparation of 19, 21
was prepared from amide 20 and ketoaldehyde 17 in 33% yield
(58% brsm, [crude material was a 4:1 mixture of diastereomers,
but only the major diastereomer was isolated after chromatog-
raphy13]) followed by reduction of both azides and the terminal
alkene to give 22 in 73% yield (Scheme 2).
ACKNOWLEDGMENTS
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We gratefully acknowledge North Carolina State University for
generous start-up support. Mass spectra were obtained at the
Mass Spectrometry Laboratory at NC State University.
REFERENCES
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In conclusion, we have developed a synthetic approach to the
unusual and heavily oxidized morpholinone heterocycle
contained in monanchocidin A. These initial studies have
revealed key insights into the chemical properties and stability
of these heterocycles and pave the way for their further study.
Exploration into the role of these scaffolds in biology,
particularly as probes to explore polyamine signaling path-
ways,14 is ongoing and will be reported in due course.
ASSOCIATED CONTENT
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S
* Supporting Information
(6) Additional product was not observed if the reaction was allowed
to proceed for longer reaction times; however, if purified 9 was
resubjected to the reaction conditions amide 7 was observed (∼25%
after 18 h) suggesting that the reaction is reversible and may reach
equilibrium under the employed conditions.
Experimental procedures, characterization of products, 1H, 13C,
and 2D-NMR spectra are provided. This material is available
(7) A comparison of the 1H and 13C NMR data of our natural
product fragment (22) to that of the morpholine region of 1 is
presented in the Supporting Information.
AUTHOR INFORMATION
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Corresponding Author
(8) Tentative assignment as this compound was not stable to
Notes
isolation and purification.
(9) (a) Tidwell, T. T. Org. React. 1990, 39, 297. (b) Tojo, G.;
Fernandez, M. Oxidation of alcohols to aldehydes and ketones: a guide to
current common practice; Springer: New York, NY, 2006.
The authors declare no competing financial interest.
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