L. Azéma et al.51 synthesized various
D-fructose analogues modified at C-1 or C-6 positions from D-glucose as probes
for import studies by the hexose transporter in parasites e. g. Trypanosoma brucei by taking advantage of the Amadori rearrangement or
using the aldol condensation between dihydroxyacetone phosphate and appropriate
aldehyde catalyzed by fructose 1, 6-diphosphate aldolase from rabbit muscle. Rabbit muscle aldolase (EC 4.1.2.13)
reversibly catalyzes the formation of fructose 1, 6-diphosphate from two
triose-phosphates: dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate.
This enzyme which is rather selective towards the dihydroxyacetone phosphate
structure accepts a large variety of aldehydes as substrate and is frequently
in use for synthetic purposes.52 Thus, the expected
fructofuranosides (102-105) were
chemoenzymatically synthesized starting from (R)-3-azido-2-hydroxypropanal diethyl acetal (101) (Scheme 19).53 Aldol
condensation of 2-fold excess of aldehyde, resulting from deprotection of ketal
(101), with dihydroxyacetone
phosphate (formed in situ from fructose 1, 6-diphosphate) catalyzed by aldolase
(1 mmol scale) gave the ketose-phosphate which was hydrolyzed in presence of
acid phosphatase to yield 6-azido-6-deoxy-fructose (102) as unique reaction product. Subsequent ketalization of the
azido ketose gave the corresponding methyl fructofuranoside (103) as a mixture of α- and β-forms.
This compound allowed to obtain 6-amino-6-deoxy-fructose derivative (104), isolated after reductive
amination, finally, sulfonylation of the ammonium salt with dansyl chloride,furnished the uorescent α- and
β-methylfructofuranosides, 105a and 105b respectively. Attempts to obtain 105(a, b), through fructose derivative
(107) starting from aldol
condensation between dansyled (R) 3-amino-2-hydroxy-propanal diethylacetal
106 (obtained from 101) and dihydroxyacetone phosphate
catalyzed by aldolase (Scheme 19) were unsuccessful. This is likely due to
either the poor solubility of the aldehyde in aqueous solution or to the
possible enzyme inactivation when high level of organic cosolvent was used to
make the aldehyde soluble.
____________
51. L. Azéma, F. Bringaud, C. Blonski,
J. Périé, Bioorg. Med. Chem., 2000, 8, 717.
52. (a) C.-H. Wong, F. P. Mazenod, and
G. M. Whitesides, J. Org. Chem., 1983, 48, 3493; (b) M. D. Bednarski, E. S. Simon, N. Bischofberger, W.-D.
Fessner, M.-J. Kim, W. Lees, T. Saito, H.
aldmann, and G. M. Whitesides, J. Am.
Chem. Soc.,
1989, 111, 627; (c) J. M. Gijsen, L. Qiao, W. Fitz, and C.-H. Wong, Chem Rev., 1996, 96, 443.
53. a) P. Page, C. Blonski, and J. Périé, Tetrahedron, 1996, 52, 1557. b) T. Gefflaut,
C. Blonski, J. Périé, and M. Willson, Prog.Biophys. Molec. Biol., 1995, 63,301; (c) J. Périé, I. Rivére-Alric, C. Blonski, T. Gefflaut, N. Lauth de
Viguerie, M. Trinquier, M. Willson, F. R. Opperdoes, and M Callens, Pharmac. Ther., 1993, 60, 347; (d) T. Gefflaut, C. Blonski, and
J. Périé, Bioorg. Med. Chem. 1996, 4, 2043; (e) C. Blonski, D. De Moissac,
J. Périé, and J. Sygusch, Biochem. J.,1997, 323, 71.
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