L-fucose analogs

NaBH4 reduction with the help of CeCl3 -7H20 to obtain threo derivatives 232 (O Scheme 61). An enzymatic route for the synthesis of L-fucose analogs modified at the non-reducing end is reported by Fessner et al. [86], Using 2-Hydroxy-2-methylpropanal 233 and dihydroxyacetone phosphate 234 as substrates, branched fucose derivative 237 has been prepared via recombinant L-fuculose 1-phosphate aldolase (FucA) and L-fucose ketol isomerase (Fuel) in E. coli (O Scheme 62). 

R,3R) for rhamnose isomerase and (2S,3R) for fucose isomerase1861. A sequential application of Fuc 1-P aldolase and fucose isomerase was employed for the preparation of L-fucose analogs [98L... 

Fessner et al.[256] developed an efficient method for the synthesis of L-fucose analogs modified at the nonpolar terminus by means of L-fucose isomerase and l-fuculose 1-phosphate aldolase from E. coli. Various L-fucose analogs bearing linear or branched aliphatic side chains were prepared in about 30% overall yield with hydroxyaldehyde precursors and dihydroxyacetone phosphate as the starting materials (Fig. 17-32). 

Figure 17-32. Enzymatic synthesis of L-fucose analogs with L-fucose 1-phosphate aldolase (FucA), phosphatase (P ase), and L-fucose isomerase (Fuel). Reprinted from Fessner et al.l2561.

Combination of FucA and fuculose isomerase for the synthesis of interesting L-fucose analogs having tails with increased hydrophobicity and reactivity (Fessner et al. 2000). Homologues and unsaturated analogs of L-lactaldehyde were well tolerated by FucA with high diasteromeric excess (> 95%). 

Figure 10.26 Short enzymatic synthesis of L-fucose and hydrophobic analogs, and of L-rhamnose, by aldolization-ketol isomerization, including kinetic resolution of racemic hydroxyaldehyde precursors.

In the methods outlined above, none of the deoxypentoses were isolated they were characterized as crystalline 2-benzyl-2-phenylhydrazones or as phenylosazones. Except for the synthesis of the l-lyxo analog,219 which may conveniently be prepared from L-fucose, all of the other methods have been replaced by more practical approaches. 

Methyl-L-fucose has been prepared in an analogous manner to that of its enantiomorph by the methylation of methyl 3,4-isopropylidene-o-L-fucopyranoside,71,76 followed by hydrolysis. 

By analogy to results obtained in studies on the biosynthesis of dTDP-L-rhamnose,18 dTDP-6-deoxy-L-talose,17 and GDP-L-fucose,41 it seems very likely that dTDP-6-deoxy-L-/yxo-hexos-4-ulose (21), formed by the 3,5-epimerase reaction, remains enzyme-bound. 

Luengo, J I, Gleason, J G, Synthesis of C-fucopyranosyl analogs of GDP-L-fucose as inhihitors of fucosyltransferases. Tetrahedron Lett., 33, 6911-6914, 1992. 

Applying an analogous method, Kobayashi and Kawasuji [37] have prepared L-fucose from (C)-crotonaldehyde and the ketene acetal 83 in four steps and 49% overall yield (Scheme 13.34). The asymmetric aldol condensation is catalyzed by a complex made of Sn(OTf)2 and chiral diamine 84. 

U. B. Gokhale, O. Hindsgaul, and M. M. Palcic, Chemical synthesis of GDP-fucose analogs and their utilization by the Lewis a-l,4-fucosyltransferase. Can. J. Chem. 65 1063 (1990). 

Human a-l,3-fucosyltransferases are found in milk,51 53 saliva,54 and other specific cell lines.55-57 Through cloning studies, a role for an a-1,3-fucosyltransferase in cell adhesion was identified for the biosynthesis of sialyl Lewisxon neutrophils.58-59 As these studies link a-l,3-fucosyltransferase to cell adhesion and since the activated fucose species used by this enzyme is GDP-L-fucose, Luengo, et al.,eo prepared the C-glycoside analog of GDP-fucose shown in Figure 1.4.4. 

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