ChemComm
Communication
T. Washio, N. Shimada, S. Kitagaki, M. Nakajima, M. Shiro and
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¨
8 For a review, see: (a) C. F. Nising and S. Brase, Chem. Soc. Rev., 2008,
Scheme 3 Total synthesis of (Æ)-diospongin A.
´
37, 1218. For selected examples, see: (b) L. Ferrie, L. Boulard,
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The efficiency of this 4-step [3+2+1] synthetic strategy for THPOs
was further demonstrated by a concise diastereoselective total
synthesis of (Æ)-diospongin A (Scheme 3). Due to the interesting
biological activity, a number of elegant strategies have been devel-
oped for the racemic and asymmetric total synthesis of diospongins
A and B.21 Our synthesis began with preparation of a,b-unsaturated
isoxazoline 9 through 3 high yielding steps: Dess–Martin oxidation
of allylic alcohol 8, oxime formation and [3+2]-cycloaddition with
styrene. Chemoselective reductive ring opening of isoxazoline 9 was
performed to give the crude b-hydroxyenone which was used
directly without purification for intramolecular 6-endo-trig oxa-
Michael cyclization. Desilylation and Dess–Martin oxidation of
the crude tetrahydropyran-4-one gave the diketone 10 as a major
diastereomer in 37% yield over 4 steps, which was reduced
chemoselectively with K-selectride in THF at À78 1C to furnish
the (Æ)-diospongin A in 64% yield. In the course of our synthesis,
only four chromatographies were required for 8 steps with 20.2%
overall yield. All spectroscopic data for our synthetic sample are in
well agreement with that of the reported natural product.15
We have developed a short and highly flexible [3+2+1] synthetic
strategy for the synthesis of substituted tetrahydropyran-4-ones
with high diastereoselectivity, featuring 1,3-dipolar cycloaddition
of a,b-unsaturated nitrile oxides, SmI2-promoted chemoselective
reductive ring opening of isoxazolines and Amberlyst-15 mediated
6-endo-trig oxa-Michael cyclization. This synthetic strategy was
successfully applied in the concise diastereoselective total
synthesis of (Æ)-diospongin A in 8 steps with 20.2% overall
yield, and would find applications in the synthesis of other
tetrahydropyran-4-ones and natural products.
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10 Direct aldol reaction of aldehyde and enone gave moderate yield
with limited substrate scope, see: C. Baker-Glenn, N. Hodnett,
M. Reiter, S. Ropp, R. Ancliff and V. Gouverneur, J. Am. Chem.
Soc., 2005, 127, 1481. It is noted that Lee developed an efficient
route for synthesis of 2,6-tetrahydronpyran-4-one using in situ gen-
eration of b-hydroxyenones from b-hydroxy allyl ketones. See: A. S.-Y.
Lee, L.-S. Lin and Y.-T. Chang, Tetrahedron, 2012, 68, 3915.
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15 See ESI†.
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c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 193--195 195