L-fuculose 1-phosphate

It is well known that the 1-phosphates of the ketoses, L-fuculose (51) and L-rhamnulose (52) have considerable biochemical interest. Their chemical synthesis has not been described as far as is known to the writer, but the rate of acid hydrolysis of L-fuculose 1-phosphate, obtained by enzymatic synthesis, has been determined by Heath and Ghalambor (20) and that of L-rhamnulose 1-phosphate by H. Sawada (48) and by Chiu and Feingold (II). They found that the rate of... 

This enzyme [EC 4.1.2.17] catalyzes the aldol cleavage of L-fuculose 1-phosphate to yield glycerone phosphate and (5 )-lactaldehyde. 

D-fructose 1,6-bisphosphate 2 (FruA E.C. 4.1.2.13), D-tagatose 1,6-bisphosphate 4 (TagA E.C. 4.1.2.40), L-fuculose 1-phosphate 5 (FucA, E.C. 4.1.2.17), and L-rhamnulose 1-phosphate 4 (RhuA, E.C. 4.1.2.19). From previous studies, we have DHAP aldolases with all four possible specificities readily available, we have demonstrated their broad substrate tolerance for variously substituted aldehydes, and we have investigated their stereoselectivity profile with non-natural substrates [3-6]. 

W. D. Fessner, G. Sinerius, A. Schneider, M. Dreyer, G. E. Schulz, J. Badia, and J. Arguilar, Diastereoselective enzymatic aldol additions L-Rhamnulose and L-fuculose 1-phosphate aldolases from E. coli, Angew. Chem, lnt. Ed. Engl. 30 555 (1991). 

While the lyases that transfer a pyruvate unit form only a single stereogenic center, the group of dihydroxyacetone-phosphate-(DHAP, 41)-dependent aldolases create two new asymmetric centers, one each at the termini of the new C-C bond. A particular advantage for synthetic endeavors is the fact that Nature has evolved a full set of four stereochemically-complementary aldolases [189] (Scheme 6) for the retro-aldol cleavage of diastereoisomeric ketose 1-phosphates— D-fructose 1,6-bisphosphate (42 FruA), D-tagatose 1,6-bisphosphate (43 TagA), L-fuculose 1-phosphate (44 FucA), and L-rhamnulose 1-phosphate (45) aldolase (RhuA). In the direction of synthesis this formally allows the... 

Table 5. Substrate tolerance of L-rhamnulose 1-phosphate and L-fuculose 1-phosphate aldolases [195,347]...

In vivo, six known DHAP-dependent aldolases are known to catalyze the reversible enanotioselective aldol addition of dihydroxyacetone phosphate to an acceptor aldehyde. The group is comprised of fructose 1,6-diphosphate (FDP) aldolase (EC 4.1.2.13), L-fuculose 1-phosphate (Fuc 1-P) aldolase (EC 4.1.2.17), tagatose 1,6-diphosphate (TDP) aldolase (EC 4.1.2.2), ketotetrose phosphate aldolase (EC 4.1.2.2), L-rhamnulose 1-phosphate (Rha 1-P) aldolase (EC 4.1.2.19), and phospho-5-keto-2-deoxygluconate aldolase (EC 4.1.2.29). The in vivo catalyzed reactions of this group are shown in Scheme 5.3. 

Water-in-oil gel emulsions were tested in enzymatic aldolization of selected N-Cbz-amino aldehydes (Figure 19.3), N-Cbz-3-amino propanal (4), N-Cbz-glycinal, (5), (S)-N-Cbz-alaninal (6), and (R)-N-Cbz-alaninal (7) catalyzed by RAMA and L-rham-nulose-1-phosphate aldolase (RhuA) and L-fuculose-1-phosphate aldolase (FucA) from Escherichia coU [27,28]. The largest differences between conventional dimethyl formamide (DMF)/water co-solvent systems and gel emulsions were observed with RAMA and FucA catalysts (Figure 19.3). The emulsion media enhanced the catalytic efficiency of RAMA towards the N-Cbz amino aldehydes tested three, five. 

Figure 13-7 Interaction of the bound zinc ion of L-fuculose-1-phosphate aldolase and catalytic side chains with the substrate in the active site of the enzyme as revealed by X-ray crystallography and modeling. See Dreyer and Schulz. ...

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). 

Although many aldolases have been characterized for research purposes, these enzymes have not been developed commercially to any significant extent. This is likely due to the availability of the various biocatalysts and the need for dihydroxyacetone phosphate (DHAP) (44), the expensive donor substrate required in nearly all aldolase reactions. A number of chemical and enzymatic routes have been described for DHAP synthesis, which could alleviate these concerns [12], In terms of the enzyme supply issue, this may change with the introduction of products from Boehringer Mannheim and their Chirazyme Aldol reaction kit. They have three kits, each containing a different aldolase fructose-1,6-diphosphate FruA) (EC 4.1.2.13), L-rhamnulose-1-phosphate RhuA (EC 4.1.2.19), and L-fuculose-1-phosphate (FucA) (EC 4.1.2.17). As more screening... 

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). 

These systems were tested in the enzymatic aldolization of a variety of A/-Cbz-aminoaldehydes catalyzed by D-fructose-l,6-bisphosphate aldolase from rabbit muscle (RAMA) and L-rhamnulose-1-phosphate aldolase and L-fuculose-1-phosphate aldolase from E. coli (Espelt et al. 2003 a,b, 2005). The largest differences between conventional DMF/water cosolvent systems and gel emulsions were observed with RAMA catalyst (Fig. 6.5.11). 

In context with a project aimed at structure-activity relationships of sialyl Lewis X epitope analogues, a range of new L-fucose derivatives with increased hydrophobicities of the C-5 substituents, such as compounds 124 and 126, was recently synthesised [100] employing Fessner s proven L-fuculose 1-phosphate aldolase/L-fucose isomerase protocol (Scheme 38). 

L-Fuculose 1-Phosphate from OL-Lactaldehyde by Racemate Resolution [171]. Racemic lactaldehyde dimethylacetal (6.0 g, 50 mmol) in 50 mL water was hydrolyzed by treatment with cation-exchange resin (Dowex AG50W-X8, H+ form) at 60 °C for 8 h. After filtration, an aqueous solution... 

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