Communications
[a]2D2 = + 1388 (c = 0.55, 95% EtOH)[2f]), and 1H and
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Chem. 2004, 43, 4441; Angew. Chem. Int. Ed. 2004, 43, 4341.
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[12] Although removal of the N-2,4-dimethoxybenzyl group in 31,
leading to tirandalydigin (2), was examined under various
conditions, this transformation has not been successful so far
because of the susceptibility of the vinyl epoxide moiety to acidic
conditions. We will discuss the removal of the protective group in
detail in a full paper.
13C NMR, IR, and mass spectra.[2f]
The crucial construction of the tetramic acid moiety for
the total synthesis of tirandalydigin was performed by
employing the protocol of Ley et al.[11] Thus, initially,
streptolic acid (3) was converted into keto thiolester 28 in
two steps: 1) treatment with SOCl2 leading to the acid
chloride and 2) condensation of the acid chloride with 27 by
the use of NaH in THF (79% for two steps). Upon treatment
of 28 with N-2,4-dimethoxybenzyl glycine ethyl ester (29),
Et3N, and silver trifluoroacetate in THF, the desired product
30 was obtained in 95% yield; this product was then treated
with TBAF in THF to afford the target compound, N-2,4-
dimethoxybenzyl tirandalydigin (31), in 89% yield.[12] The
synthesis of 31 was unambiguously confirmed by its spectral
1
data, including the H and 13C NMR, IR, and mass spectra.
The total yield of 31 was 9.8% (an average of 94% yield for
each step) in 37 steps from the starting material 7.
In summary, we have developed a new and promising
synthetic methodology for the synthesis of the tetramic acid
family of antibiotics and have completed the first synthesis of N-
2,4-dimethoxybenzyl tirandalydigin (31), as well as the synthesis
of streptolic acid (3), in a highly stereoselective manner.
Received: October 14, 2004
Published online: January 28, 2005
Keywords: antibiotics · asymmetric synthesis · methylation ·
.
natural products · stereoselectivity
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