L-Noviose (11), which can be found not only in the
coumarin antibiotics but also (in modified form) in lipiar-
mycin,9 was the subject of many synthetic approaches. It
was made as an enantiomerically pure compound starting
from D-glucose,10 L-arabinose,11 L-rhamnose,12 and D-ribose13
and from a sugar building block (obtained from furfural).14
On the other side, noviose was obtained as a racemic mixture
from 2-acetylfuran as a nonsugar starting material.15
diazomethane in diethyl ether17b,18 resulted in the formation
of the key intermediate 7 (an enantiomer of the previously
described R-D-lyxofuranosiduronic acid derivative17b); it was
prepared in 66% overall yield for the last three steps.
The ester 7 was treated with a variety of Grignard reagents
and transformed to the tertiary alcohols 8a-c (Scheme 2).
We have chosen commercially available D-gulonolactone
3 as a starting material and transformed it by the known
reaction sequence to isopropylidene derivative 416 (Scheme
1). Periodate cleavage17 of 4 in a mixture of water and
Scheme 2a
Scheme 1a
a Reagents and conditions: (a) RMgCl, Et2O; (b) H2, 10%
Pd/C, Et2O.
In the next step, benzyl protection group19 was removed by
the catalytic hydrogenation to give 4-O-demethyl-L-novio-
furanose derivative 9a [2,3-O-(1-methylethylidene)-5,5-di-
C-methyl-R-L-lyxofuranose] and related propyl 9b or phenyl
9c derivatives. To our knowledge, 9a is the first example of
a noviofuranose derivative containing an unsubstituted ano-
meric hydroxy group. Namely, it was reported previously
that anomeric methoxy group was cleaved under strong acidic
conditions to give the corresponding pyranosyl derivative;
thus, concomitant ring transformation of the furanoid to the
pyranoid form occurred.12 In our case, under neutral condi-
tions in diethyl ether as a solvent, this ring-ring conversion
was not feasible. An X-ray diffraction study of the compound
9a (Figure 1) revealed its R-L-lyxofuranosyl structure and a
a Reagents and conditions: (a) NaIO4, MeOH, H2O (73%); (b)
AgNO3, KOH, EtOH, H2O (92%); (c) CH2N2 in ether (99%).
methanol gave an aldehyde 5, which was oxidized with
Ag2O17 into the acid 6. A subsequent esterification with
(4) Zhang, M. Q.; Haemers, A. Pharmazie 1991, 46, 687.
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Musicki, B. Bioorg. Med. Chem. Lett. 1999, 9, 2875. (c) Ferroud, D.;
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Bonnefoy, A.; Musicki, B. Bioorg. Med. Chem. Lett. 1999, 9, 2881. (d)
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Hamelin, C.; Mauvais, P.; Lassaigne, P.; Bonnefoy, A.; Musicki, B. Bioorg.
Med. Chem. Lett. 2000, 10, 161. (e) Musicki, B.; Periers, A.-M.; Laurin,
P.; Ferroud, D.; Benedetti, Y.; Lachaud, S.; Chatreaux, F.; Haesslein, J.-
L.; Iltis, A.; Pierre, C.; Khider, J.; Tessot, N.; Airault, M.; Demassey, J.;
Dupuis-Hamelin, C.; Lassaigne, P.; Bonnefoy, A.; Vicat, P.; Klich, M.
Bioorg. Med. Chem. Lett. 2000, 10, 1695. (f) Schio, L.; Chatreaux, F.; Klich,
M. Tetrahedron Lett. 2000, 41, 1543. (g) Peixoto, C.; Laurin, P.; Klich,
M.; Dupuis-Hamelin, C.; Mauvais, P.; Lassaigne, P.; Bonnefoy, A.; Musicki,
B. Tetrahedron Lett. 2000, 41, 1741. (h) Boehm, H.-J.; Boehringer, M.;
Bur, D.; Gmuender, H.; Huber, W.; Klaus, W.; Kostrewa, D.; Kuehne, H.;
Luebbers, T.; Meunier-Keller, N.; Mueller, F. J. Med. Chem. 2000, 43,
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Figure 1. ORTEP plot of 4-O-demethyl-L-noviofuranose 9a.
(9) Arnone, A.; Nasini, G.; Cavalleri, B. J. Chem. Soc., Perkin Trans. 1
1987, 1353.
(10) (a) Vaterlaus, B. P.; Doebel, K.; Kiss, J.; Rachlin, A. I.; Spiegelberg,
H. Experientia 1963, 19, 383. (b) Vaterlaus, B. P.; Doebel, K.; Kiss, J.;
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twist form (with C-4 endo and O exo) of the furanosyl
skeleton. We would also like to mention that the pyranose
analogue of 9a, reported in ref 12 (compound 6), has physical
data distinctly different from the data for 9a described in
2652
Org. Lett., Vol. 5, No. 15, 2003