L-Fucose-1-phosphate

This enzyme [EC 2.7.7.30] catalyzes the conversion of GTP and L-fucose 1-phosphate to yield GDP-L-fucose and pyrophosphate (or, diphosphate). 

A de novo synthesis of GDP-Fuc (13), UDP-Gal (16) and UDP-GalNAc (19) by isolated enzymes of the salvage pathways (see Fig. 14) has not yet been described. A crude extract from porcine submaxillary glands gave a yield of 80% for the synthesis of p-L-fucose-1-phosphate (12), but the synthesis of 13 was less successful with a yield of 20% [312]. The main pathways for 16 and 19 involve 4-epimerases (Table 4 and Fig. 14) which are not suitable for preparative synthesis due to their unfavourable equilibrium constants [347, 348], An alternative is Gal-l-P uridyltransferase which is only specific for Gal-l-P and GalNH2-l-P (Table 4). 

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.

Several rare ketose 1-phosphates have been obtained by use of L-rhamnulose kinase on the corresponding ketoses which were, in turn, available by isomerization of the appropriate 2R- or 25-aldoses (D-ribose, L-lyxose, L-mannose, L-talose, D-glucose, D-allose, L-rhamnose, L-fucose) with L-rhamnose- or L-fucose-isomerase, respectively. P-L-Fucose 1-phosphate and the thermodynamically less stable p-anomer of GDP-fucose were accessible by use of enzymatic processes. A new, simple, chemical preparation of rhamnulose 1-phosphate from L-rhamnose is outlined in Scheme 5. ... 

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). 

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). 

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). 

The in situ generation of GDP-Fuc from P-fucose-1-phosphate coupled with the transfer of the fucose moiety on to A -acetyllactosamine has also been probed on an analytical scale [96]. In the presence of GTP P-fucose-1-phosphate is converted to GDP-Fuc by GDP-fucose pyrophosphorylase. GDP-Fuc is then used by an a(l-3)fucosyl transferase to transfer the fucose moiety on to A -acetyllactosamine. The released GDP is recycled and phosphorylated to give GTP by a phosphokinase with phosphoenol pyruvate as phosphate source. The pyrophosphate produced in the complete cycle is decomposed by pyrophosphatase (see Scheme 16). 

Fig. 7.—Elution Pattern for Lotus Extracts from L-Fucosyl-agarose. [Initial elution with 0.01 M sodium phosphate in saline, followed by elution with 0.1 M L fucose in 0.01 M phosphate buffer in saline (arrow) (see Ref. 20).]...

Fructose bisphosphate aldolases 699 Fructose 6-phosphate 535, 693s Fructose 6-phosphate kinase 656 Fructose-1,6-bisphosphatase 645 Fructose-2,6-bisphosphatase 646 Fruit fly. See Drosophilia melanogaster Fucose (Fuc) 165s L-Fucose isomerase 693 Fucosyltransferase 184 Fucoxanthin 22... 

Fig. 14. Salvage pathways of nucleotide sugars. L-fucose (11), (3-L-fucose-l-phosphate (12), GDP-p-L-fucose (13), A fucokinase (EC 2.7.1.52), B GDP-Fuc pyrophosphorylase (EC 2.7.7.30). D-galactose (14), a-D-galactose-l-phosphate (15), UDP-a-D-galactose (16), C galactokinase (EC 2.7.1.6), D UDP-Gal pyrophosphorylase. IV-acetyl-D-galactosamine (17), Al-acetyl-a-D-galactosamine-l-phosphate (18), UDP-lV-acetyl-a-D-galactosamine (19), E IV-acetyl-galactosamine kinase (EC 2.7.1. ), F UDP-GalNAc pyrophosphorylase (EC 2.7.7. )...

GDP-ot-D-mannose (23) is the donor substrate for mannosyltransferases [139, 146, 338-340] and the precursor of GDP-(3-L-fucose (13) [173,197, 243, 341], Based on the work of Munch-Petersen [342, 343], only crude extracts from yeast have been used for the enzymatic synthesis of labeled and unlabeled 23 and GDP-deoxymannose derivatives (Table 4) [303-305, 307, 308, 344-346] as well as for the in situ regeneration of 23 (Table 4). Common to all these approaches is the use of chemically synthesized sugar-1-phosphates as substrates for GDP-Man PP. An obvious disadvantage of using crude yeast enzyme preparations is the poor quality of the enzyme source since only fresh cells or certain batches of baker s yeast are suitable for synthesis [304, 307], GDP-Man PP was purified from pig liver and used for the synthesis of 8-Azido-GDP-Man however, the enzyme lacks absolute specificity for GDP-Man in the pyrophos-phorylysis reaction [309]. 

This pattern of reactivity at C(l) of aldopyranosyl derivatives was first quantitated by O Connor and Barker (1979), who studied the hydrolyses of aldopyranosyl phosphates at acid pH, the reaction is an SN1 departure of phosphate monoanion. Equatorial/axial rate ratios of 2.3 for glucose (cf. [1] and [2]), 1.9 for L-fucose [10], 2.3 for D-galactose [11] and 4.1 for D-mannose... 

Simple chemical syntheses of GDP-fucose (1) and its analogs 2 and 3 were devised which involved the direct reaction of a-pyranosyl bromides with tetrabutylammonium dibenzylphosphate (Figure 2) (22), These displacement reactions were carried out with protected derivatives of the parent L-fucose, 3-deoxy-L-fucose and D-arabinose (the 6-demethyl analog of L-fucos because of the relative ease of preparation of the required glycosyl bromides. The p-phosphates thus obtained were coupled with GMP-morpholidate to yield the GDP derivatives 1-3. 

---