S. A. Bennett, R. W. Rickards / Tetrahedron Letters 44 (2003) 6927–6930
6929
Scheme 4. Cyclisation of the 4-deoxy- -xylulose-b-ketodecanoate 13c.
D
derived by Knoevenagel condensation from the keto-
form 13c (Scheme 4).
based approach for providing analogues of the natural
elicitor that could be useful in elucidating its mecha-
nism of action.
The least polar product,11 isolated in 16% yield, was
not UV active. Comparison of NMR spectra of this
compound with those of syringolide 2 5b1,2 confirmed
that it was 4%-deoxysyringolide 2 14. Signals characteris-
tic of the tricyclic syringolide system were observed (in
Me2CO-d6) at lH 3.11 (s, H2) and at lC 59.9 (C2), 86.6
Acknowledgements
We thank Dr J. P. Henschke for helpful discussion, Ms
J. M. Rothschild for mass spectrometry, and Mr. A. J.
Herlt for technical assistance.
1
(C3%), 99.4 (C2%), and 108.5 (C3). The H spectrum of
the deoxy analogue differed significantly from that of
syringolide 2 only in that the H4% methylene protons
appeared as a multiplet between l 1.92–1.97, shifted
upfield from the H4% methine doublet of doublets at l
4.13 in the natural compound. A corresponding upfield
shift of C4% itself from l 75.4 to l 39.5 was also
observed.
References
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The more polar isomer,12 isolated from the cyclisation
reaction in 8% yield, was UV active. Its NMR spectra
were unlike those of 4%-deoxysyringolide, and defined
the structure as that of the diacyl butanolide 15. The
13C spectrum displayed the lactone carbonyl at l 170.4
(C1), ketonic resonances at l 201.3 (C3) and 206.3
(C3%), and methine resonances at l 48.2 (C2%) and 54.0
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(C2). In the H spectrum a four spin system linked the
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geminal H1% protons at l 4.54 (t, J 8.9 Hz) and 4.33
(dd, J 8.9 and 7.7 Hz) to the H2% proton at l 4.20 (ddd,
J 8.9, 8.1 and 7.7 Hz) which in turn was coupled to the
H2 resonance at l 4.06 (d, J 8.1 Hz). The assignments
together with structure 15 were confirmed by HMQC
and HMBC data. A NOESY correlation between H2
and H2% indicates their cis-relationship, in agreement
with their mutual coupling constant of 8.1 Hz.13
This diacyl butanolide 15 clearly arises under the basic
conditions by enolisation and subsequent ketonisation
of the initial Knoevenagel condensation product, the
deoxy analogue of the acyl butenolide 4b. Its formation
shows that, at least in the case of the 4-deoxyxylulose
b-ketoester 13c, there is a discrete alternative process
competing with the later stages of the triple cyclisation.
This process may help to explain the low yields
observed in the original biomimetic synthesis of
syringolide 2 5b.
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The facile formation of 4%-deoxysyringolide 2 14 by
cyclisation of the 4-deoxyxylulose b-ketodecanoate 13c
indicates that the occurrence and stereospecificity of the
7. 5c; 1H NMR (300 MHz, CD3OD) l 1.64 (3H, s, H4),
3.09 (1H, s, H2), 3.87 (1H, dd, J 10.1 and 2.7 Hz, H5%a),
3.99 (1H, d, J 10.1 Hz, H5%b), 4.15 (1H, d, J 2.7 Hz, H4%),
4.46 (1H, d, J 10.5 Hz, H1%a), 4.47 (1H, s, H3%), 4.76 (1H,
d, J 10.5 Hz, H1%b); 13C NMR (75 MHz, CDCl3) l 25.8
(C4), 62.7 (C2), 75.4 (C1% or C5%), 76.2 (C4%), 77.3 (C1% or
biomimetic triple cyclisation of the corresponding
D-
xylulose ester 3b to syringolide 2 5b are not dependent
upon the presence of the 4R-hydroxyl group. Further-
more, it reinforces the utility of the biomimetically-