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hydroxy groupat C6 with ( R)-9-phenyl-6-methyl-4-nonenoic
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total synthesis of zaragozic acid C (1).
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In conclusion, we have accomplished a highly convergent
and stereocontrolled total synthesis of zaragozic acid C in 30
steps (longest linear sequence) and 3.7% overall yield from
di-tert-butyl d-tartrate (4). The synthesis illustrates the power
of the carbonyl ylide cycloaddition methodology for rapidly
assembling the unique 2,8-dioxabicyclo[3.2.1]octane core and
the olefin cross-metathesis methodology to construct the C1
alkyl side chain. Importantly, the strategy is flexible with
other types of ylides and potentially allows for the introduc-
tion of a variety of nonnatural heteroatomic substituents into
the core structure. The synthesis of such analogues for
biological and pharmacological investigations is currently
underway.
[12] O. Kataoka, S. Kitagaki, N. Watanabe, J. Kobayashi, S. Naka-
mura, M. Shiro, S. Hashimoto, Tetrahedron Lett. 1998, 39, 2371 –
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Received: August 12, 2003 [Z52629]
[13] For a carbonyl ylide cycloaddition approach to L-740,758, a
product of the oxidative photodegradation of zaragozic acid A,
see: H. Koyama, R. G. Ball, G. D. Berger, Tetrahedron Lett.
1994, 35, 9185 – 9188.
[14] For synthetic studies of zaragozic acids by a carbonyl ylide
cycloaddition–rearrangement strategy, see: a) D. M. Hodgson,
J. M. Bailey, T. Harrison, Tetrahedron Lett. 1996, 37, 4623 – 4626;
b) D. M. Hodgson, C. Villalonga-Barber, Tetrahedron Lett. 2000,
41, 5597 – 5600; c) D. M. Hodgson, J. M. Bailey, C. Villalonga-
Barber, M. G. B. Drew, T. Harrison, J.Chem.Soc.Perkin Trans.1
2000, 3432 – 3443.
[15] G. Uray, W. Lindner, Tetrahedron 1988, 44, 4357 – 4362.
[16] In this case it would be preferable to obtain the 1,2-diol;
however, reduction of 5 under Saito conditions (BH3·SMe2,
NaBH4, THF) did not work: S. Saito, T. Ishikawa, A. Kuroda, K.
Koga, T. Moriwake, Tetrahedron 1992, 48, 4067 – 4086.
[17] Use of solvents other than CH2Cl2 led to a significant decline in
diastereoselectivity: THF, 59%, 2.2:1; Et2O, 64%, 3.2:1; toluene,
62%, 4.3:1.
Keywords: carbonyl ylides · cycloaddition · diazo compounds ·
.
metathesis · total synthesis
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5354
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Angew. Chem. Int. Ed. 2003, 42, 5351 –5355